FISIOLOGI SISTIM REPRODUKSI

dr. ANIS KUSUMAWATI, M.Sc., M.Med.Ed

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Fully developed male & female external genitalia
 SISTIM PRERPODUKSI

• Organ reproduksi laki-laki dan perempuan bekerja bersama untuk menghasilkan

keturunan
• Reproduksi seksual: proses organisme menghasilkan keturunan melalui
pembentukan gamet (sel sperma dan ovum)
• Kelompok organ reproduksi sesuai fungsinya
– Gonad: testis dan ovarium menghasilkan gamet dan hormon seks
– Duktus: mentransport gamet
– Kelenjar seks asesoris: menghasilkan substansi yang melindungi gamet dan
memfasilitasi gerakan
– Struktur pembantu: penis dan uterus: membantu fungsi gamet

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 ANATOMI ALAT REPRODUKSI

ALAT REPRODUKSI LAKI-LAKI TERDIRI DARI :

 ALAT REPRODUKSI EXTERNA: SKROTUM, PENIS

 ALAT REPRODUKSI INTERNA: TESTIS, EPIDIDIMIS, VASA DEFFERENS, VESICULA
SEMINALIS, PROSTAT, URETRA.

ALAT REPRODUKSI WANITA TERDIRI DARI :

 ALAT REPRODUKSI EXTERNA: VULVA, LABIA MAYORA, LABIA MINORA, CLITORIS,

MONS PUBIS, GLANDULA VESTIBULARIS MAJOR DAN MINOR
 ALAT REPRODUKSI INTERNA: VAGINA, UTERUS, TUBA FALLOPII, OVARIUM.

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GENETALIA PRIA

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 PENIS

• Bekerja sebagai alat untuk mengeluarkan urin (air seni), cairan semen
(ejakulat) dan untuk kopulasi.
• Bentuk silindrik, terdiri dari 2 bagian: corpus cavernosum (ada 2) dan corpus
spongiosum (ada 1).
a. Corus cavernosum : ¾ bagian distal, terdiri dari jaringan erektil
terbungkus di dalam jaringan fibrous yang kuat. Ke arah proximal
menempel pada ramus inferior ossis pubis. Bagian proximal ini
membentuk crus penis (2 kanan dan 2 kiri). Jaringan fibrous sebelah
anterior membentuk septum penis.
b. Corpus spongiosum: terdiri dari jaringan erektil. Bagian anterior
membesar, menutupi ujung anterior corpus cavernosum dan disebut
sebagai glans penis. Corona gladis adalah bagian glans yang paling
lebar. Bulbus penis letaknya menempel pada diaphragma urogenital.
Seluruhnya ditembus/dilalui oleh urethra.

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• Kulit: tipis, tidak berbulu, subcutisnya tidak berlemak. Sebagian menutupi sampai
melampaui glans penis disebut sebagai praeputium penis.

• Pembuluh darah :
1. Arteri : cabang-cabang arteri pudenda interna di dalam diphragma urogenitale.
a. A. dorsalis penis, menembus diphragma urogenitale disebelah anteriornya, terletak
di kanan dan kiri v. dorsalis penis, subfascialisnya tertutup oleh fascia penis
profundus.
b. A. profunda penis di diaphragma urogenitale, memasuki crura penis dan terletak di
dalam corpus cavernosum.
c. A. bulbaris menuju bulbus urethrae.
2. Vena: berasal dari trabecula di dalam corpus cavernosum.
a. Superficial: dari preputium penis, berjalan subcutan dan bermuara ke dalam v.
pudenda externa.
b. Profundus: dari jaringan cavernosus ke vena dorsalis penis subfascialis, ke v.
perinealis dan v. iliaca interna.

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Organ genetalia pria: externa dan interna (1)

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Organ genetalia pria: externa dan interna (2)

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Organ genetalia pria externa: scrotum dan penis

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 SCROTUM

• Suatu kantong dengan dinding tipis, terdiri dari cutan dan subcutan.
• Lapisan kulit pigemennya berminyak, berkerut-kerut. Sub cutannya berisi
serabut-serabut otot polos: tunica dartos yang mengatur suhu testis.
• Fascia spermatica externa: lanjutan m. obliquus abdominis externus.
• M. cremaster: lanjutan m. obliquus abdominis internus.
•Processus vaginalis peritonei: lanjutan peritoneum parietalis, setelah
menutup disebut ligamnentum vaginale. Pada testis memecah menjadi 2 :
periorchium dan epiorchium

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 TESTIS
• Sepasang, di dalam scrotum. Kiri lebih berat dari yang kanan.
• Ukurannya: 41/2x21/2x2 cm
•Lapisan luarnya: tunica albuginea, sebelah dalam membentuk septula,
diantaranya diisi tubuli seminiferi contorti. Dari tubuli seminiferi contorti
tubuli recti rete testis vassa efferentes epididimis (caput,
corpus, cauda) menuju ductus defferens.
•Fungsi: pembentukan spermatozoa (spermatogenesis) dan pembentukan
hormon testosteron. Hormon ini mempengaruhi tanda-tanda sex sekunder
pada pria dan fertilitas (kesuburan).

EPIDIDIMIS
• Vassa efferens bersaatu disini, berbelok-belok, mengarah ke corpus makin
lurus, dan setelah cauda epididimis menjadi ductus deferens.
• Terjadi pematangan spermatozoa
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Organ genetalia interna pria

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Testis dan saluran sperma

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Spermatogenesis

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Spermatozoa berumur 5 minggu

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• Testicle has two function/activities :
– Steroidogenesis
– Spermatogenesis

• Tubulus seminiferous is the part of testicle placed of

spermatogenesis
 Spermatogenesis
Merupakan proses terus menerus dalam 3 tahap:
1. Produksi sel gamet
• Embriogenesis awal, germ cells primordial migrasi terdapat di tubulus
seminiferus testis
• Sel akan berkembang menjadi spermatogonia
• Spermatogonia tidak aktif sampai pubertas. Ketika pubertas akan
membelah terus menerus dengan mitosis, jumlahnya bertambah
menghasilkan sel baru
2. Diferensiasi fungsional untuk fertilisasi
• Beberapa sel berhenti membelah dan berdiferensiasi menjadi
spermatosit primer
• Setiap spermatosit primer mengalami pembelahan meiosis
menghasilkan 2 spermtosit sekunder
• Ketika pembelahan kedua lengkap terbentuk 4 spermatid haploid
3. Diferensiasi struktural agar lebih motil
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 MITOTIC DIVISION

MEIOTIC DIVISIONS

TRANSFORMATION
PIF

MITOTIC DIVISION

MEIOTIC DIVISIONS

TRANSFORMATION

Copied from Lucinda L.

An Atlas of Human Gamet and Conceptus
Testicular Compartmentalization
Sertoli Cell Function
Spermatogenesis: Sperm Production in the Testis
Spermatozoa Structure and Functions in Review
Palermo et al., 1997
Regulation of Spermatogenesis
Testicular Cell Interactions
Hypothalamic-Pituitary regulation of Testicular Function
Male Sex Steroid Synthesis
Major Testicular Steroids
Testosterone from birth…..
Testosterone level
 DUCTUS DEFERENS

Terdiri dari 3 bagian: pars abdominalis, pars inguinalis, pars scrotalis.

Keluar dari anulus inguinalis praeperitonealis, membelok ke mediodorsal, menyilang arteri
illiaca externa pada sebelah ventralnya, berjalan diantara ureter dan vesica urinaria, medial dari
vesicula seminalis, menuju ke basis prostat. Disini melebar, namanya ampulla. Menggabung
dengan saluran dari vesicula seminalis, menjadi ductus ejaculatorius, menembus prostat,
bermuara ke dalam urethhra menjadi colliculus seminalis.

VESICULA SEMINALIS

Kantong bergelembung kecil-kecil, menempel pada bagian postero-inferior vesica urinaria,

kaudal dari bagian ureter dan ductus deferens bermuara bersama dengan ductus deferens ke
dalam pars prostatica urethrae. Kelenjar ini menghasilkan cairan seminal yang kental (bagian
dari cairan semen).

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 PROSTAT

• Suatu kelenjar yang terdapat pada kaudal dari vesica urinaria, mempunyai capsula, sebesar
buah duku.
• Berlobus 5: anterior, 2 lateral, posterior dan medius.
• Mengandung banyak jaringan ikat dan otot polos.
• Basisnya menghadap ke vesica urinaria, apexnya mengarah ke diaphragma urogenital.
• Terpisah dari rectum oleh excavatio rectovesicalis.
• Anterior terpisah dari symphisis pubis karena adanya plexus venosus praevesicalis.
• Dilalui oleh urethrae (pars prostatica)
• Pada dinding lumen terdapat colliculus seminalis. Pada puncak coliculus ini terdapat utriculus
prostatrica/vagina maskulina.
• Cekungan di kanan dan kiri colliculus dinamakan sinus prostaticus.
• Di kanan dan kiri utriculus prostaticus bermuara ductus ejaculatorius. Pada sinus prostaticus
bermuara saluran-saluran kelenjar prostat.
• Kelenjar ini menghasilkan cairan encer seperti susu, mengandung banyak asam
phosphatase (konsentrasi dalam darah tinggi, pada karsinoma prostat)

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Kelenjar prostat dan kantong kemih

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Sintesis hormon steroid laki-laki

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GENETALIA WANITA

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 GENETALIA INTERNA

OVARIUM
• Ada 2, kanan dan kiri
• Organ yang menghasilkan telur (ovum), juga merupakan kelenjar endokrin
karena menghasilkan hormon yang mempengaruhi pertumbuhan genetalia
externa dan mengatur terjadinya menstruasi.
• Letaknya pada dinding lateral pelvis
• Homolog dengan testis.

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Organ genetalia wanita: externa dan interna

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 TUBA UTERINA (FALLOPII)

• Merupakan saluran yang fungsinya membawa ovum dari ovarium ke cavum uteri (ruang
dalam uterus).
• Ada 2 kiri dan kanan, terbagi atas (dari lateral ke medial) :
a. Infundibulum ( + fimbrae)
b. Ampulla (tempat tersering terjadinya pembuahan)
c. Isthmus
d. Pars uterina tubae (bagian tuba yang masuk ke dalam dinding uterus)

UTERUS (RAHIM)

• Adalah organ berongga dengan dinding muskuler tebal, terletak dalam cavum pelvis minor
antara vesica urinaria (disebelah ventral) dan rectum (disebelah dorsal).
• Fungsinya untuk tempat nidasi ovum yang telah dibuahi sampai aterm.
• Bentuk seperti buah pir, dengan dinding ventral dan dorsal saling berimpit.
• Ukuran : panjang 7½, lebar 5 cm, tebal 2½ cm
• Posisi uterus normal anteversi dan antefleksi.

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Bagian-bagian uterus :

1. Fundus: bagian uterus yang terletak cranial dari garis yang menghubungkan ke dua
osteum tuba.
2. Corpus: adalah bagian yang terpenting dari uterus, di dalamnya terdapat cavum uteri,
yang dalam keadaan tidak hamil pipih dalam arah antero-posterior dan berbentuk
segitiga.
3. Isthmus: bagian yang menyempit setelah corpus, yang dibagian dalam sesuai dengan
osteum uteri internum.
4. Cervix uteri (leher rahim): bagian uterus mulai dari osteum uteri internum sampai osteum
uteri externum dan berhubungan dengan vagina.

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Organ genetalia wanita interna

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Uterus

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 VAGINA

• Adalah organ berbentuk tabung, yang berfungsi untuk: alat kopulasi, jalan
kelahiran, jalan keluar darah menstruasi.
• Dinding sangat elastis.
• Menghubungkan uterus dengan dunia luar dan bermuara ke
dalam vestibulum vaginae pada lubang yang disebut introitus
vagianae.
• Arterialisasi: dari arteri vaginalis.

HYMEN (SELAPUT DARA)

• Adalah lipatan mucosa yang menutupi sebagian dari introitus vagina.

• Bentuknya bermacam-macam: hymenanularis, hymen elastica, hymen
cribiformis, hymen lobatus, semilunaris, fimbriatus dll
• Sisa-sisa hymen disebut caruncula hymenalis. 51
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GENETALIA EXTERNA WANITA
MONS PUBIS
• Adalah daerah dengan peninggian dibagian median, di depan symphisis pubis
• Sebagian besar terisi jaringan lemak
• Setelah pubertas, tertutup kulit berambut.

LABIUM MAJUS
• Homolog dengan scrotum
• Merupakan dua lipatan memanjang (kanan dan kiri), berjalan ke caudodorsal dari mons pubis
dan menutupi rima pudendi.
• Bagian luarnya tertutup kulit yang mengandung banyak pigmen, banyak kelenjar lemak.
Setelah pubertas tertutup kulit berambut.
• Permukaan dalam licin dan tidak berambut.
• Kedua labium majus ke ventral bertemu, tempat pertemuan ini disebut: comisura anterior.
• Ke arah dorsal tidak menggabung, tetapi bagian centrum tendineum perinei masuk ke rima
pudendi, disebut: comisura posterior.
• Dibawah kulit, terdapat jaringan ikat subcutan yang sebagian besar terdiri dari lemak,
beberapa berkas otot polos, saraf, pembuluh darah dan limfa.

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Organ genetalia externa

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 LABIUM MINUS

• Adalah 2 lipatan kulit kecil, terdapat diantara kedua labia majora.

• Tiak mengandung jaringan lemak, permukaannya licin, basah dan berwarna merah muda.
• Kedua labium minus membatasi suatu celah, yang disebut vestibulum vaginae.
• Kesebelah ventral, lipatan kulit pecah menjadi 2 (medial dan lateral). Yang bagian lateral
bertemu di sebelah cranial clitoris, disebut praeputium clitoridis. Yang bagian medial bertemu
di sebelah caudal clitoris disebut Frenulum clitoridis.
• Ke arah dorsal kedua labium minus bertemu, disebut Frenulum labii.

VESTIBULUM VAGINAE
• Adalah celah antara kedua labium minus.
• Berisi: introitus vaginae, urethrae pada orificium urethrae externa, orificium dari glandula
vestibularis major (greater vestibular gland).
• Orficium urethrae externa, terletak dorsal dari clitoris dan tepat ventral dari introitus vaginae.
• Fossa navicularis, adalah cekungan di vestibulum vaginae, antara introitus vaginae dengan
frenulum labii.

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 CLITORIS
• Homolog denga penis
• Merupakan jaringan erektil, tidak dilalui urethrae
• Terdiri dari: 2 crura clitoridis, yang melekat pada ramus inferior ossis ischii bagian dalam. 2
corpora cavernosa clitoridis (letaknya caudal dari symphisis pubis) menjadi corpus clitoridis,
glans clitoridis.

BULBUS VESTIBULI
• Homolog dengan penis
• Merupakan massa memanjang dari jaringan erketil, pada sisi lateral introitus vaginae,
terbungkus m. bulbo cavernosus, barjalan sampai glans clitoridis.

GLANDULA VESTIBULARIS MAJOR

• Ada sepasang, bentuk bulat/ovoid
• Letaknya tepat dorsal atau tertutup bagian posterior bulbus vestibuli.
• Muaranya terdapat pada celah antara labium minus dengan batas perlekatan hymen.
• Homolog dengan glandula bulbourethralis pada pria.
• Kelenjar ini tertekan selama coitus, sehingga mengeluarkan sekresi mukus yang berfungsi
untuk lubrikasi bagian distal vagina.
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Proses konsepsi

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Fertilisasi

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Pertumbuhan hasil konsepsi (hari ke 14)

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Pertumbuhan hasil konsepsi (minggu ke 4)

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Pertumbuhan hasil konsepsi (minggu ke 4)

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Pertumbuhan hasil konsepsi (minggu ke 5)

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Pertumbuhan hasil konsepsi (minggu ke 8)

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Pertumbuhan hasil konsepsi (minggu ke 10)

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Placenta

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Pertumbuhan hasil konsepsi (minggu ke 16)

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Pertumbuhan hasil konsepsi (genap bulan)

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Persalinan kala I (pembukaan)

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Persalinan kala I (pembukaan lengkap)

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Persalinan kala II (pengeluaran janin)

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Persalinan kala III (pengeluaran placenta)

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Glandula mammae untuk proses laktasi

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Masa pertumbuhan

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 MENSTRUASI
SIKLUS MENSTRUASI
• Fase: menstruasi, proliferasi dan sekretori
• Berhubungan dengan fase folikuler dan luteal dari
siklus ovarium
• Fase menstruasi (hari ke 1-5)
• Fase proliferasi (hari ke 5-14)
• Fase sekretori (hari ke 14-28)

SIKLUS MENSTRUASI: siklus endometrium, ovarium,

servikal/ vaginal
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Perubahan histologi di endometrium selama siklus ovulasi
• Tujuan 2/3 lapisan fungsionalis endometrium adalah untuk
persiapan implantasi blastokist
• Tempat tersebut merupakan tempat proliferasi, sekresi dan
degenerasi
• Tujuan 1/3 lapisan basalis adalah untuk menyediakan untuk
regenarasi endometrium setelah hilangnya lapisan fungsional
saat menstruasi

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Pengaturan fase proliferasi dan diferensiasi

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 Fase proliferasi
• Disebabkan oleh kenaikan kadar ß-estradiol (E2)
• Terjadi mitosis di sel epitel dan stroma
• Jaringan menebal menyeluruh
• Pertumbuhan kelenjar (pseudostratified)

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 Fase sekretori awal
• Dimulai saat hari ovulasi
• Terjadi kenaikan progesteron luteal
• Vakuola sekretori sub nuklear berkembang dalam
epitel kelenjar (hari ke 14-20)
• Kelenjar menjadi corkscrew-shape, stroma
mendapatkan vakuola

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• Estrogen dalam konsentrasi rendah menyebabkan pituitari
anterior menyekresi sedikit FSH dan LH sebagai respon
terhadap GnRH dan juga menghambat neuron hipotalamus
yang menyekresi GnRH
• Inhibin bekerja di pituitari untuk menghambat sekresi FSH
• Estrogen meningkat drastis menyebabkan pituitari anterior
menyekresi lebih banyak LH dan FSH sebagai respon
terhadap GnRH. Estrogen juga merangsaang neuron
hipotalamus untuk menyekresi GnRH
• Konsentrasi progesteron plasma yang tinggi menghambat
neuron hipotalamus menyekresi GnRH

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 Sel granulosa
• Menutrisi oosit
• Menyekresi chemical mesenger yang mempengaruhi
sel oosit dan teka dalam mengontrol perkembangan
folikel selama fase folikuler awal dan pertengahan
• Mengekspresikan aromatase yang mengubah
androgen menjadi estrogen
• Menghasilkan inhibin yang menghambat sekresi FSH
melalui aksinya di pituitari
• Tempat kerja induksi LH dalam mengubah oosit dan
folikel saat ovulasi dan pembentukan korpus luteum

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 HORMON
(estrogen, progesteron, FSH, LH, inhibin, prolaktin, oksitosin)

PERAN ESTROGEN
• Dalam sistim reproduksi:
– Pertumbuhan organ reproduksi
– Siklus M: folikulogenesis dan oogenesis
– Siklus vaginal
– Kehamilan laktasi
• Non reproduksi:
– Otak, kulit, ginjal, pertumbuhan, metabolisme
deposit klasium, kardiovaskuler

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• PERAN PROGESTERON
– Siklus menstruasi
– Siklus vagina
– Implantasi-kehamilan
– Laktasi

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• Ovarian structure :
– Fixed no germ cell (oocytes)
– Weeks 22 gestation --- 7 millions immature oocytes
– Birth---2 millions oogonia
– Puberty each ovary weigh 5-10 g
– Only 500 oocytes will become mature rest die (atretic)

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• Activin enhances FSH biosinthesis and secretion,
and participates in the regulation of the menstrual
cycles
• Activin is produced in the gonads, pituitary gland,
placenta
• Activin increases FSH binding and FSH-induced
aromatization
• It participates in androgen synthesis enhancing LH
action in the ovary

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• AMH is expressed by granulosa cell during the
reproductive years
• Controls the formation of primary follicles by
inhibiting excessive follicular recruitment by FSH
• Role in folliculogenesis
• From 25 y.o AMH declines to undetectable levels at
menopause

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pengaruh hormon

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– Non reproductive system
• Brain
• Skin
• Kidney
• Growth
• Metabolism
• Deposition of Ca
• Cardiovascular

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• FSH
• LH
• Inhibin
• Prolactin
• Oxytocyn

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• Progesterone
– Menstrual cycle
– Vaginal cycle
– Implantation-pregnancy
– Lactation

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 Oogenesis

• Ovum production
• Occurs monthly in ovarian follicles
• Part of ovarian cycle
– Follicular phase (preovulatory)
– Luteal phase (postovulatory)

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Oogenesis

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The Ovarian Cycle

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The Ovarian Cycle

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The Uterine Tubes

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 The uterus

• Muscular organ
– Mechanical protection
– Nutritional support
– Waste removal for the developing embryo and fetus
• Supported by the broad ligament and 3 pairs of
suspensory ligaments

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 Uterine wall consists of three layers:
• Myometrium – outer muscular layer
• Endometrium – a thin, inner, glandular mucosa
• Perimetrium – an incomplete serosa continuous with
the peritoneum

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The Uterus

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The Uterus

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The Uterine Wall

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The Uterine Wall

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 Uterine cycle
• Repeating series of changes in the endometrium
• Continues from menarche to menopause
– Menses
• Degeneration of the endometrium
• Menstruation
– Proliferative phase
• Restoration of the endometrium
– Secretory phase
• Endometrial glands enlarge and accelerate their rates of
secretion

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The Uterine Cycle

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 Gonads
• Gonads produce gametes as well as gonadal
hormones.
• In the male, the interstitial cells located among
the seminiferous tubules, called Leydig cells,
produce testosterone.
• In the female, the granulosa cells of the follicle
produce E2 and after ovulation the theca interna
and granulosa cells make up the CL and
produce P4.

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 Hormones of the Gonads
• Two classes of steroid hormones produced by the
ovaries are estrogens and progestins
– Steroid hormones are synthesized from cholesterol, a
27 carbon steroid.
– Steroid hormones are carried in the circulation by
binding proteins such as albumin or SBG.

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 Steroid Hormones
• Steroid hormones have a common molecular nucleus
called the cyclopentanoperhydrophenanthrene
nucleus. This molecule is composed of 3 six member
fully hyrdogenated phenanthrene rings and a one
member cyclopentane ring.

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 Steroid Hormones
• Cholesterol is converted to pregneneolone, a 21 C
progestagen by the enzyme cytochrome P450 side
chain cleavage. This cleaves off part of the chain of
cholesterol leaving a 21 C pregneneolone.
• Pregneneolone (P5) is converted to progesterone (P4)
by a dehydrogenase and isomerase enzyme.
• P4 is converted to testosterone by a 17,20 desmolase
enzyme.

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 Steroid Hormones
• Testosterone is converted to estradiol (E2) by a complex of
enzymes known as aromatase.
• Steroids with 21 C have progestagenic activity, 19 C have
androgenic or glucocorticoid activity, and 18 C have estrogenic
activity.
• Estrogens consist of estradiol, estrone, and estriol. Estradiol is the
primary estrogen produced by the ovary.
• Estrogenic compounds found in plants are known as isoflavones,
found in legumes (genistein & coumesterol). Zearalenone is an
estrogenic compound produced by mold.

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 Progestagens
• Progesterone is the most prevalent progestagen and
is secreted by the CL, placenta, and adrenal gland.
• P4 prepares the endometrium for implantation and
maintenance of pregnancy by increasing secretory
activity and by inhibiting motility of the myometrium.
• P4 acts synergistically with estrogens to induce estrus
behavior.
• P4 develops the alveoli of the mammary gland
• High levels of P4 inhibits estrus and the ovulatory
surge of LH.
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 Estrogens
• Produced by specific cells in the graffian follicle
– Thecal cells of the follicle are stimulated by LH to
produce androgens with diffuse across the basement
membrane where they are converted to estrogens by
granulosa cells under the influence of FSH
• Estrogens consist of estradiol, estrone, and estriol.
Estradiol is the primary estrogen produced by the
ovary

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 Estrogens
• Estrogens act on the CNS to cause behavioral estrus
in the female, act on the uterus to increase the
amplitude and frequency of contractions by
potentiating actions of oxytocin and PGF2a, cause
physical development of 2o sex characteristics,
stimulate duct growth and development of the
mammary gland, exert positive and negative feedback
on LH and FSH through the hypothalamus.

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 Androgens
• Testosterone is an androgen produced by Leydig cells and the
adrenal cortex but it is not the most potent.
• Testosterone is converted to dihydrotestosterone (DHT) which
binds to the nuclear receptor.
• Testosterone stimulates late stages of spermatogenesis, promotes
growth, development and secretory activity of the accessory sex
glands.
• Testosterone maintains 2o sex characterisitics and libido of male.

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 Hormone-Receptor Signalling
• For protein & peptide hormones - receptor is in
plasma membrane.
• For steroid hormones - receptor is in nucleus
• For prostaglanding hormones - receptor is in
plasma membrane.

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 Hormone-Receptor Signalling
• Receptors have a specific affinity or degree of attraction for a
specific hormone.
• Receptors for protein hormones are an integral part of the plasma
membrane. They can contain distinct regions such as the
extracellular domain, transmembrane domain, and the intracellular
domain.
• Concentration of receptor sites in a target organ will increase or
decrease depending on the endocrine status of the animal.

127
 Hormone-Receptor Signalling
• Hormonal potency is influenced by receptor density and hormone
receptor affinity.
• Hormonal agonists are analogs which bind to the specific receptor
initially and cause the same biological effects as the native hormone.
Some promote a greater physiological activity due to increased
affinity.
• Hormone antagonists have a greater affinity for the hormone
receptor but promote weaker biological activity by occupying
receptors and preventing the native hormone from binding.

128
 Other Hormones
• Inhibin is a glycoprotein hormone that contains an a
and one of two possible b subunits.
• Inhibin is made by granulosa cells in the ovary and
by Sertoli cells in testes. It inhibits the release of
FSH.

129
 Other Hormones
• Activin is a protein found in follicular fluid that
consists of 2 b subunits.
• Activin causes the release of FSH in cultured
pituitary cells but it’s function has not been
demonstrated in the intact animal.

130
 Placental Hormones
• Placental hormones are identical to or have
similar activity to other hormones.
• eCG – equine chorionic gonadotropin is a
glycoprotein hormone with a & b subunits similar
to LH and FSH and it has mostly FSH activity.
• eCG has a longer ½ life (several days) than FSH
due to increased sialic acid content.

131
 Placental Hormones
• eCG is made by the endometrial cups that are
formed ~ d 40 of pregnancy and last until ~ d 85.
• eCG stimulates development of ovarian follicles
which become luteinized due to LH like activity.
These accessory CL’s produce P4 to maintain
pregnancy in the mare.

132
 Placental Hormones
• hCG- human chorionic gonadotropin is made by the
synctiotrophoblastic cells of the primate placenta.
• hCG is a glycoprotein consisting of a and b chains with
a MW ~ 40,000. a subunit is similar to the a subunit
of human, porcine, ovine, and bovine LH. b subunit
has 145 amino acids and 5 carbohydrate chains.
• It’s presence is urine in early pregnancy is the basis
for early pregnancy tests.

133
 Prostaglandins
• PG’s were first discovered in seminal plasma of
mammallian semen and was believed to
originate from the prostate.

• All PG’s are 20 carbon unsaturated hydroxy fatty

acids derived from arachidonic acid. At least 6
PG’s exist and numerous metabolites with a
wide range of physiological activity exist.

134
135
 Prostaglandins
• PG’s are not synthesized by any particular tissue
but travel in the blood to a target tissue. Some
forms never appear in the blood and others are
degraded by the lungs and the liver.
• PG’s cause contraction of smooth muscle in the
reproductive and GI tracts, erection, ejaculation,
sperm transport, ovulation, and regression of the
CL.

136
 Hormonal Secretion
• Hormones are secreted in 3 types of patterns,
episodic, basal (tonic) and sustained.
• Episodic is associated with hormones under
nervous control such as when nerves in
hypothalamus “fire”, neuropeptides (GnRH) are
released in sudden bursts. Hormones from the
AP tend to be released in this manner.

137
138
 Hormonal Secretion
• Basal or tonic secretion is where the hormone
fluctuates with low amplitude pulses.
• Sustained release is where the hormone remains
elevated but in a relatively steady state for a long
period of time. Steroids tend to be secreted this
way.

139
 Hormonal Feedback

• Hormonal feedback can be either positive and

cause a continued release of the hormone
(preovulatory surge) or negative (luteal phase) and
decrease the release of the hormone.
• Feedback can occur at three different levels and is
termed: ultra-short feedback, short feedback, and
long feedback.

140
 Hormonal Feedback
• Ultra-short feedback is where the releasing factors or
hormones (GnRH) are released from the
hypothalamus and feeds back directly to the
hypothalamus to decrease it’s own secretion.
• Short feedback is where the releasing factors or
hormones causes the release of the AP hormones,
which feedback and inhibit the further release of
releasing hormones from the hypothalamus.

141
 Hormonal Feedback
• Long feedback is where secretion of the releasing
hormone hormone is inhibited by the increased
secretion of steroid hormones from the gonad.

142
Female feedback Diagram

143
 Hormone-Receptor Activation
Gland Hormone Chemical Principal Functions
Class
Ovary Graafian Estrogens Steroid Mating behavoir, Secondary , sex characteristics,
Follicle (Estradiol) maintenance of female duct system, Mammary
growth
Inhibin Protein Regulates release of FSH from anterior pituitary
(Folliculostatin)

Corpus Progestins Steroid Maintenance of pregnancy, Mammary growth &

Luteum (Progesterone) secretion

Relaxin Polypepti Expansion of pelvis

de Dilation of cervix

144
 Hormone-Receptor Activation
Gland Hormone Chemical Principal Functions
Class
Placenta Human Glycoprotein LH-like - Involved with gonadotropin (HCG)
Chorionic establishment of pregnancy in human
Support and maintain CL
Endometri Equine Glycoprotein FSH-like- some LH activity Old name - Pregnant
al Cups Chorionic Mare Serum Gonadotropin (PMSG) Immunological
Gonadotropin protection of foal Mare during pregnancy Formation
(eCG) of accessory CL in mare

Estrogens/Pro Steroids Regulate placental bloodflow

gestins Maintenance of pregnancy

145
 Hormone-Receptor Activation
Gland Hormone Chemical Class Principal Functions
Endometrial Cups
Relaxin Protein Relaxation/dialation of
cervix for parturition
Placenal Lactogen Glycoprotein Stimulates mammary
growth & milk secretion.
Uterine Endometrium
Graafian FoAllicles
Seminal Vesicles
Prostaglandin F2a (PGF2a) Lipid Regression of CL Stimulate
myometrial contractions
Ovulation Sperm transport

146
 Reproductive Endocrinology in the Female

Functions and Structural Organization of the Ovary

Neuroendocrine Regulation of Ovarian Functions
Regulation of Ovarian Steroid Production
Actions of Estradiol and Progesterone
Follicle Development, Ovulation, and Luteinization
Oogenesis and Oocyte Maturation
The Menstrual Cycle
Endocrinology of Pregnancy, Parturition, and Lactation

147
 Functions of the Ovary

• Production of a mature oocyte, capable of fertilization and

embryonic development.
• Production of ovarian steroids (estradiol, progesterone).
• Production of gonadal peptides (inhibin, activin).

148
 Structural Organization of the Ovary

• The main functional unit of the ovary is the

follicle.
• Follicles are composed of the oocyte, granulosa
cells, and theca cells.

149
 Stages of Follicular Growth

• Follicles are present in a number of different

stages of growth:
- primordial follicles (resting)
- primary, secondary, and antral follicles
- preovulatory (Graafian) follicles

150
 The Corpus Luteum

• After the preovulatory follicle ovulates

(releases its egg), it forms the corpus luteum.

151
Neuroendocrine Regulation of Ovarian Functions

CNS
hypothalamus
GnRH
Pituitary

LH FSH Follicle
Development
E2, P
Ovulation
inhibin, OVARY
Luteinization
activin
152
 Effects of GnRH on Gonadotropins

• GnRH is released in a pulsatile manner, stimulating the

synthesis and release of LH and FSH.
• GnRH acts through its receptor on the pituitary gonadotroph
cells, stimulating production of phospholipase C.
• Recall that IP3 pathway causes gonadotropin release, while
the DAG/PKC pathway causes gonadotropin synthesis.

153
Actions of FSH on Granulosa Cells
FSH



AC

ATP
Gs
Gene Expression
cAMP
steroidogenic
enzymes
PKA LH Receptor
Inhibin Subunits
Plasminogen
activator
CREB CRE
154
 Regulation of Estradiol Production

• Recall the two-cell theory of estradiol production:

- LH acts on theca cells to produce androgens
- FSH acts on granulosa cells to increase aromatase activity,
resulting in conversion of androgens to estrogens

155
 Ovarian Estradiol Production

LH
Theca cells androgens

aromatase

Granulosa cells
FSH estradiol

156
 Regulation of Progesterone Production

• Progesterone is produced from theca cells, mature granulosa

cells, and from the corpus luteum.
• In this case, gonadotropins induce expression of
- steroidogenic acute regulatory protein
- P450 side chain cleavage

157
 Actions of Estradiol

• Estradiol plays an important role in feedback regulation of

gonadotropin release.
• Low estradiol levels exert negative feedback (via inhibition
of GnRH release)

158
 Actions of Estradiol

• High estradiol levels exert positive feedback (via increase in

GnRH receptors, stimulation of GnRH release, increased
pituitary response to GnRH, and effects on LHb)
-increase in stimulatory neurotransmitters regulating GnRH
neurons (ie, norepinephrine)
- decrease in inhibitory neurotransmitters (ie, beta endorphin)
- increased activity of GnRH neurons
- increased expression of GnRH receptors
- increased expression of LHb gene

159
 Actions of Estradiol
• Estradiol also has important actions in a number of other tissues:
- causes proliferation of uterine endometrium
- increases contractility of uterine myometrium
- stimulates development of mammary glands
- stimulates follicle growth (granulosa cell proliferation)
-effects on bone metabolism, hepatic lipoprotein production,
genitourinary tract, mood, and cognition
• Effects are mediated through the intracellular estrogen receptors
(alpha and beta), and possible membrane effects.

160
 Actions of Progesterone

• Progesterone exerts positive and negative feedback effects

on gonadotropin synthesis and release.
• Progesterone also acts on many tissues:
- stimulates secretory activity of the uterine endometrium
- inhibits contractility of the uterine myometrium
- stimulates mammary growth
• The actions of progesterone are mediated through an
intracellular P receptor, which acts as a transcription factor.

161
 Regulation of Follicle Growth

• Primordial follicles can “rest” for many decades before being

recruited for growth by an unknown mechanism.
• The recruitment of primordial follicles and subsequent
growth to the small antral follicle stage can occur without
gonadotropin stimulation (gonadotropin-independent).
• Small antral follicles (and larger) must be stimulated by FSH
and LH in order to continue growth to the preovulatory stage
(gonadotropin dependent).

162
 Regulation of Follicle Growth

• Each day many follicles begin to grow (recruitment).

• Each cycle, only one follicle is “selected” for continued
development to the preovulatory stage, by an unknown
mechanism.
• This follicle is called the dominant follicle
• The remaining recruited follicles become atretic and
degenerate.

163
 Regulation of Follicle Growth

recruitment selection

preovulatory
follicle

atresia

164
 Follicular Ovulation

• As the preovulatory follicle grows, it produces increasing

amounts of estradiol.
• When the preovulatory follicle is mature, plasma estradiol
levels are very high.
• High estradiol levels exert positive feedback on the
hypothalamus and pituitary, resulting in LH and FSH surges.
• These preovulatory gonadotropin surges cause ovulation of
the preovulatory follicle (follicular rupture and release of the
egg for fertilization).

165
Mechanism of Gonadotropin-induced Ovulation

• The preovulatory LH and FSH surges induce expression of

enzymes in the preovulatory follicle which break down the
follicle wall.
• Tissue-type plasminogen activator: results in breakdown of
fibrin.
• Metalloproteinases: result in breakdown of collagen.
• Result: follicle wall is ruptured, resulting in release of the
oocyte into the peritoneal cavity.

166
 Formation of the Corpus Luteum

• After the follicle ovulates, the remaining granulosa cells and

theca cells luteinize.
• Luteinization: accumulation of cholesterol and lipid, cells
swell.
• Luteinized cells switch the ovary from predominant
production of estradiol to production of progesterone and
estradiol.
• This prepares the uterine endometrium for pregnancy.

167
 Summary of Meiosis
(for a single chromosome)

168
 Oogenesis and Oocyte Maturation

• Recall that germ cells must go through meiosis in order to

produce unique haploid cells.
• From one spermatogonia, end up with four spermatozoa.
• Oocytes must also go through meiosis, but they do it during
the course of follicular development.
• Primordial follicles contain primary oocytes that are arrested
in prophase I, prior to the first meiotic division (diploid).

169
 Oocyte Maturation
• Oocytes remain in prophase I until the preovulatory surge of
LH, which initiates completion of the first meiotic division.
• The primary oocyte does not split into two cells, but instead
gives off a very small first polar body, containing half of the
chromosomes.

LH surge

zona pellucida first polar1b7o0dy

 Oocyte Maturation
• Thus, the ovulated “egg” is actually not completely mature (hasn’t
completed meiosis II).
• Maturation goes to completion only if the oocyte is fertilized.
• Fertilization causes completion of meiosis II, and expulsion of a
second polar body.
• Meiosis of the oocyte results in only one gamete.

fertilization

first polar body first polar body

second polar body171
 Endocrinology of Pregnancy

• To maintain the uterine endometrium and inhibit contraction of

myometrium, must maintain plasma progesterone levels during
pregnancy.
• Early in pregnancy, this is accomplished by the action of human
chorionic gonadotropin (hCG) on the corpus luteum (first 8 weeks
of pregnancy).
• Later in pregnancy, progesterone is produced by the placenta.

172
 Early Embryonic Development

• After fertilization, the embryo spends the first four days in the
oviduct (fallopian tube).
• The developing embryo then goes to the uterus, and implants in the
uterine endometrium on Day 6 (blastocyst stage of development).
• By day 6, the trophoblast cells of the embryo begin to produce hCG.
• In a normally developing embryo, hCG levels (in maternal
circulation) will double every 3 days, reaching peak at about 2
months of pregnancy.

173
 Actions of hCG
• hCG binds to the LH receptor in the corpus luteum,
maintaining luteal steroidogenesis during the first 8 weeks of
pregnancy.
• In addition, hCG may act to stimulate testosterone
production from the developing testes in male embryos.

174
Role of the Fetal-Placental-Maternal Unit in Steroid
Production
• Later in pregnancy, the placenta becomes the major steroidogenic
organ of pregnancy.
• However, the placenta requires maternal LDL as a source of
cholesterol for progesterone production.
• The placenta also produces estrogens during pregnancy (primarily
estriol). However, the placenta is dependent upon the maternal and
fetal adrenal as a source of androgens for aromatization to estrogen.
• Estrogens may be important in increasing uterine blood flow to the
fetus, and in the maturation of fetal organ systems.

175
 Parturition: The Process of Childbirth

• The mechanisms signaling the onset of labor are not clearly

understood, although several theories exist.
• Potential role of progesterone?:
-decreasing progesterone prior to labor would allow uterine
contractions to occur
-however, there is no decline in progesterone before labor in
humans
-some studies suggest there is a decline in uterine progesterone
receptors, resulting in decreased progesterone action, leading to
labor

176
 Potential Role of Oxytocin in Parturition?

• Oxytocin causes uterine contraction.

• However, oxytocin levels do not increase until after labor starts,
according to more recent studies.
• Oxytocin may play a role in uterine contraction following labor,
resulting in decreased blood loss.

177
 Potential Role of Relaxin in Parturition?

• Relaxin acts on the cervix, causing dilatation and softening.

• In some animals relaxin increases before labor starts.
• In humans, relaxin is high beginning early in pregnancy and stays
elevated until labor.
• Relaxin does act to soften connective tissues, such as the ligaments
connecting the pelvic bones, to allow increase in size of the birth canal.
• Relaxin also decreases uterine contractility during pregnancy.

178
 Potential Role of Prostaglandins in Parturition

• Prostaglandins cause dilation and softening of the cervix.

• Prostaglandins also cause uterine contractions.
• The levels of prostaglandins increase in fetal membranes before the
onset of labor.
• It is believed that some (unknown) signal from the fetus causes
increased prostaglandin production from fetal membranes, which then
act on the uterus and cervix to initiate labor.

179
 Lactation
• Lactation is the delivery of milk from the mammary gland.
• There are four main stages of lactation, controlled by
different hormones:
- milk synthesis in alveolar cells
- secretion of milk from alveolar cells to alveolar lumen
-maintainance of established milk production and release
into alveolar lumen
-milk ejection: movement of milk from alveoli into the duct
system and out of the breast

180