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1. List the hormones that are secreted by the testis
Testosterone (Leydig cells), inhibin (Sertoli cells)
2. Describe how secretion of the testicular hormones is regulated
T secretion by Leydig cells decreases GnRH (hypothalamus) and LH
(anterior pituitary), Inhibin from Sertloi cells decreases FSH
3. Describe the role of the hypothalamus and pituitary gland in
the regulation of spermatogenesis
4. Describe the role of the hypothalamus and pituitary gland in
the regulation of testicular steroidogenesis
5. List several causes of male infertility
vasectomy, unknown causes, past cryptorchidism

Vas deferens connects epididymis through to the prostrate gland. Testis is

the site of spermatogenesis.
Prostrate gland sits under the bladder, allows sperm to travel through vas
deferens and pick up secretions made by the prostrate.
The seminal vesicles and prostrate gland make up the secretions required
for the sperm cells to survive after ejaculation. They are known as the
accessory glands.
Steps of sexual differentiation:

The absence of SRY and TDF (signaling mechanisms) causes the

formation of ovaries. The SRY and TDF mechanisms signal the
formation of testes.
The female reproductive system is the passive or default differentiation
pathway or system. The male reproductive system is an active system
and requires its own signaling mechanisms which are the SRY and TDF

If there is a problem in the activation cascade or signaling mechanisms,

there may be problems in the formation of testes, therefore a problem
in testosterone which may cause presence of female traits despite
being male and having XY chromosomes.

Development of external Gentalia:

- Male and female genitalia looks identical at 7 weeks of gestation.
- At 10 weeks, divergence occurs and there is a difference in folding.
- Near the end of gestation, actual differences can be observed, due to
the signaling cascade being activated in the males.
Development of the reproductive tract:
- At 7 weeks, identical structures are present. There is the presence of
bipotential gland, wolfian ducts and mullerian ducts.
- SRY activation and testosterone signalling, along with mullerian
inhibition factor causes development of male reproductive system.
- Absence of signals cause the formation of ovaries and thus the
development of the female reproductive system.
The main difference in the structures of the male and female
reproductive system is the presence of seminal vesicles and prostrate
gland in the males and the presence of uterus in females. Testes and
ovaries are similar structures, as are the vas deferens and fallopian
- Sit inside the scrotum, as they are very sensitive to the body
temperature (will stop functioning in body temperature).
- Well protected within layers of muscles and blood vessels as it is the
site of testosterone and sperm production.
- Contains coiled seminiferous tubules where sperm is produced, it is
filtered through the Rete testes then transported to the tail of the
epididymis. Where they are matured and stored until ejaculation.
The testes has two compartments, the sperm producing compartment
which contains seminiferous tubules and the sertoli cells (that produce
inhibin) and the androgen producing compartment, which contains the
interstitial compartment and the leydig cells (which produce testosterone).
They are both controlled by the HPG axis.
Testosterone production:
- Leydig cells present in between seminiferous tubules produce
- Testosterone is a steroid hormone important for spermatogenesis. Its
productionis controlled by LH.
- Castrated people make little testosterone.
- levels of testosterone do not fluctuate to a great level during a males
life cycle, as opposed to the female steroid hormones, which decrease
in levels as you near menopause.
- LH binds to receptors on Leydig cell Leydig cell.
- This stimulates release of adenyl cyclase which begins a cascade of
reactions to stimulate production of cAMP.
- cAMP activates protein kinase, which in turn, activates specific
enzymes of produce testosterone.
- Second messenger cAMP, stimulates synthesis of Testosterone from

Testosterone is secreted into the plasma where it is transported bound

(95%) to sex-binding globulin

Hormonal regulation of testicular compartments:

GnRH produced in the hypothalamus. LH and FSH are produced in the

anterior pituitary gland.
If too much testosterone is produced, there is a negative feedback from
the leydig cells to the brain.
Excess testosterone causes negative feedback to both anterior
pituitary gland and the hypothalamus.
Inhibin causes negative feedback to only anterior pituitary gland.

Regulation of spermatogenesis and testosterone production:

- GnRH is released in pulses from the hypothalamus.
- GnRH stimulates secretin of FSH and LH, from the sertoli cells and the
leydig cells respectively.
- FSH causes secretion of inhibin while LH causes secretion of
- Testosterone and inhibin are negative feedback regulators of GnRH and
the gonadotropins.
- FSH and high levels of testosterone are required for spermatogenesis.

Function of Testosterone:
- Before birth: Required for the development of Male external genitalia,
Male reproductive tract, Descent of testes into scrotum (may cause
infertility otherwise)
- After birth: Testosterone secretion ceases, testes & remainder of
reproductive system remain small & nonfunctional until puberty.

During Puberty: Testosterone secretion surges, Testes enlarge &

spermatogenesis begins, Penis & scrotum enlarge, Accessory secretory
glands enlarge & begin secreting.

Action of Testosterone:
Androgenic actions: Initiation and maintenance of spermatogenesis:
Maintenance of secondary sexual characteristics: This is achieved
via the conversion of testosterone to DHT. Testosterone can also be
converted to estrogen by aromatase which is found mainly in adipose
- Anabolic actions: Testosterone increases basal metabolic rate and the
rate of protein synthesis. Increases muscle mass. Increases RBC.

Target organs of testosterone:

- In males: prostrate and testes.
- In females: breast and uterus
- In both: brain. Heart, liver and bones.

Effects of testosterone: include acne, enlargement of larynx, facial hair,

muscle bulk, deposition of fat on tummy instead of hips in males,
enlargement of penis, scrotum and prostrate., increase in bone strength
and increase in height.

Seminiferous tubules:

Site of spermatogenesis

Stimulated and regulated by gonadotropins/ anterior pituitary

Initial development involves spermatogonia that are located in the
basement membrane.
Sertoli cells are the nursing cells that provide the nourishment.

This is followed by spermiogenesis.

Spermiogenesis ( development of spermatozoa ):

- Change in shape from round shape to recognized shape with a tail.

Moves to tail of epididymis where they mature this takes around 12 to

21 days and mature sperm cells can remain fertile for about a month.
- The two testes of a human adult produce ~120 - 200 million sperm
each day.
The Sertoli cells:
- Produces inhibin, which has endocrine activity feeds back to the
pituitary and hypothalamus to FSH secretion; has paracrine activity
within the testis, on the Leydig cells; androgen binding protein
provides an androgen rich environment within the tubules; converts
testosterone to estradiol.

Blood- testes barrier:

- Sertoli cell is important for the development of spermatozoa
- Formation of tight junctions by adjoining Sertoli cells creates a separate
luminal compartment within the seminiferous tubules (BLOOD TESTIS
- The tight junctions form and re-form to allow spermatogonia to migrate
into the luminal compartment.
- Sertoli cell secretes testicular fluid which carries the spermatozoa to
the epididymis where they mature and gain motility

- The epididymis surrounds the posterior edge of the testes and is a
series of coiled tubes which monitor & adjust composition of fluid
produced by the seminiferous tubules, acts as a recycling centre for
damaged sperm, stores and protects spermatozoa while facilitating
functional maturation.
Sperm arrive as immature, non-motile spermatozoa. They take
approximately 12-20 days to move through the epididymis, after which
time, they are capable of swimming
- Immature sperm are stored in the tail of the epididymis for several
- Sperm are ejaculated from the epididymis into the ductus deferens.

Function of accessory glands:

- Secretions of the prostate (30%), seminal vesicles (60%) and bulbourethral gland together with the fluid secreted by the sertoli cells and
epididymis (10%) make up the semen.
- The bulbourethral gland secretions act as a cleansing lubricant.
- Seminal vesicles provide fructose, citric acid, prostaglandins and
fibrinogen. These provide nutrients for the sperm.
- Alkaline prostatic fluid helps to provide a neutral pH for fertilization.
Vasectomy ( male contraception):
- Vas deferens are cut and the ends are tied
- Prevents sperm from entering the ejaculate sterile semen
- Does not affect production of testosterone, so erection and ejaculation
are normal
- About 50% of men develop antibodies to sperm which causes fertility
problems if the vasectomy is reversed.

Male infertility:
- About 1:20 men are subfertile
- In about 60% of the cases, no identifiable cause is recognised
- 50% IVF treatments are done for male factor infertility. Uses
intracytoplasmic sperm injection ICSI
- Successful pregnancy now achievable in couples who previously had no
prospect of fertility decline in donor insemination.
Causes of male infertility:
Primary (~10.4%):
- Due to failure within testis either of seminiferous tubules or Leydig
cells low testosterone and high LH and FSH.
- Klinefelters Syndrome (XXY ~1.9%)
- Past Cryptorchidism (~6.4%) (undescended testes)
- Past Mumps Orchitis (~1.6%)
- Past irradiation or cytotoxics (~0.5%)
Secondary (~0.6%):
- Due to failure of pituitary or hypothalamus
low gonadotrophins (LH and FSH) and low testosterone.
- Genital Tract Obstruction (~4.1%)
- Varicocoele (~40%)
- Idiopathic (~39.8%)


1. Describe the structure and function of the female reproductive
2. Explain the complete ovarian and uterine cycles

3. Understand the hormonal mechanisms that regulate female

reproductive functions

Female reproductive system is more complex compared to male

reproductive system because they produce and release gametes, nurture
developing fetus and give birth.

Internal gentalia:

The female duct system is made up of the vagina, uterus and

uterine/fallopian tubes and they provide a passageway for conception
and birth.
Unlike the male system, the female duct system is not continuous,
there is a gap between the ovaries and the fallopian tubes.
The eggs are released into the ovaries and sucked into the fallopian
tube by the fimbrae.
Some oocytes dont manage to make it into the tube and are lost in
the peritoneal cavity.
Some eggs may get lost and result in ecto pregnancy (outside the

The vagina:
provides a passageway to eliminate menstrual fluids, receive the penis
during intercourse, expel fetus during child birth.
- It is a thin walled tube, 8-10cm long
- Both muscular (smooth muscle) and elastic
- Acidic environment helps keep the vagina free of infection but makes it
hostile to sperm. Interestingly, teenagers have not developed an acidic
environment, making them more susceptible to STDs.

The cervix is the opening of the bottom of the uterus. It needs to open to
expel babies.
The uterus:
- Hollow, thick muscular organ that receives, retains and nourishes
- Consists of the body (major region), fundus (top region) and cervix
(joins to the vagina)
- Glands in the mucosa of the cervix secrete mucous that block spread of
bacteria into uterus from vagina
- Also blocks entry of sperm except at midcycle when mucous becomes
less viscous.
- The uterine wall has 3 layers; the Perimetrium (outermost layer),
Myometrium (bulky, muscular middle layer, contracts to expel baby)
and the Endometrium (mucosal inner layer which allows for
implantation of the fertilised egg. This is the layer shed during
menstruation. )
- The endometrium in turn has two layers; the Functional layer
(Undergoes cyclic changes due to ovarian hormones and is shed during
menstruation) and the Basal layer (Unresponsive to ovarian hormones).

The fallopian tubes/ oviducts/ uterine tubes:

- Site of fertilisation.
- Receive ovulated oocytes
- Finger-like projections (fimbriae) sweep over the ovary to capture the

Muscular movements and beating cilia carry the oocyte towards the
The ovary:
- 2 small, almond shaped organs that produce female gametes (ova/
oocytes/eggs) and secrete female sex hormones (estrogen and
- Each ovary consists of the Medulla (Inside region which is highly
vascularised) and the Cortex (Outside region where follicles are
matured to release oocytes).
The ovarian cycle (events that mature an egg) ( has two phases):
- Follicular phase (d1-14): follicle growth. Ovulation occurs at the end of
this stage
- Luteal phase (d15-28): period of corpus luteum activity
- Driven by hormones released by the anterior pituitary gland
- Only 10% of women have a 28d cycle. Irrespective of cycle length,
luteal phase is normally 14d

The follicular phase:

The primordial follicle is made up of a small oocyte surrounded by a

single layer of granulosa cells.

The primary follicle is made up of a fully grown oocyte surrounded by

the zona pellucida and the single layer of granulosa cells.
The preantral follicle and the early secondary follicle has the fully
grown oocyte surrounded by layers of the granulosa cells and a single
layer of the theca cells
The early antral follicle or the late secondary follicle contains the fully
grown oocyte surrounded by the zona pellucida, followed by multiple
layers of the granulosa cells which also contain a small atrium filled
with fluid. The granulosa cells are surrounded by multiple layers of the
theca cells
The Graafian or mature follicle is similar to early antral cell, only the
antrum is larger with more fluid, more thecal cells and contains
cumulus oophorous which are some ganulosa cells connected to the

- The bulging follicle eventually ruptures the wall of the ovary and the
oocyte is released
Some women can feel ovulation as a twinge of pain
- A number of follicles are being prepared within the ovary at any one
time not sure how one follicle is selected for ovulation (fraternal twins
result when more than one is released)
- Increases in LH (and FSH) signals time for ovulation

Luteal phase:

Corpus luteum:
- Made of luteinised granulosa and theca cells.
- Rapid vascularisation of luteal cells
- The CL produces Progesterone (and some oestrogen)
- Maintenance of the CL depends on LH and, if pregnant, hCG
- If no pregnancy, CL regresses to become a Corpus Albicans, which is
the degraded CL. Stops progesterone secretion.
The atresia path involves the oocytes and follicles that were not matured
properly and their ultimate degeneration inside the ovaries.
Uterine/ menstrual cycle:

Cyclic changes of the endometrium in response to hormones;

endometrial changes are coordinated with the ovarian cycle
While the ovarian cycle is driven by hormones released by the anterior
pituitary, the uterine cycle is driven by steroid hormones released by
the ovary.

Day 1-5: Menstrual phase (menses)

- shedding of the functional layer of the endometrium
- estrogen and progesterone are low
Day 6-14: Proliferative (pre-ovulatory/follicular) phase - Rebuilding of the functional layer of the endometrium
- Proliferation/ increase of glandular, stromal and vascular endothelial
- Thickening of cervical mucous, becomes less viscous and sticky to
allow entry of sperm
- Stimulated and sustained by ovarian estrogens.
- Ovulation occurs at the end of this phase
- Under the influence of estrogen.
Day 15-28: Secretory (post-ovulatory) phase
Begins immediately after ovulation
- Proliferation ceases
- Secretory activity of glandular cells increases
- Endometrium prepares for implantation (glands enlarge, arteries
elongate, nutritious glycogen is secreted)
- Stimulated by progesterone and estrogens from corpus luteum If
fertilisation does not occur, CL degenerates. Low progesterone leads to
spasm of arteries, and low oxygen levels
- Blood enters fragmented capillaries and menses begins again
- Maintained by progesterone


GnRH ( gonadotrophin releasing hormones):

- Also known as luteinising hormone-releasing hormone (LHRH)
- Controls the reproductive cycle
- 10 amino acid peptide / hypophysiotrophic hormone
- Released from 1000s neurons within the hypothalamus in a pulsatile
- Produced in neurones in the brain (pre-optic area and mediobasal
- GnRH neurones secrete GnRH into hypophysial portal system in pulses.
The pulses are controlled by GnRH pulse generator
- GnRH pulses stimulate the synthesis and secretion of LH and FSH from
the anterior pituitary
Sex steroids:
- Androgens, oestrogens and progestogens
- Steroid hormones (lipid soluble)
- In females, androgens are produced in the ovary by thecal cells
- Androgens are converted to estrogens in the ovary by granulosa cells

- The corpus luteum of the ovary produces progesterone

- Sex steroids are also produced by the cortex of the adrenal gland
- Sex steroids have actions within the ovary and are secreted into the
peripheral circulation
- Important roles in a range of reproductive functions including production
of the gametes and feedback actions on the reproductive axis
- In females, oestrogens exerts negative or positive feedback effects
- Progesterone exerts only negative feedback effects

- Includes the Luteinising Hormone (LH) and Follicle Stimulating Hormone
- Heterodimeric polypeptides (-subunit and -subunit linked by disulfide
- -subunit is common to both LH and FSH
- -subunit is unique and confers biological specificity
- Gonadotrophins are synthesised and stored in gonadotroph cells in the
anterior pituitary
- Gonadotrophins are secreted into the peripheral circulation
- LH secretion is pulsatile while FSH secretion is not pulsatile (passive)
- Gonadotrophins act on the gonads to stimulate the production of the
gametes (sperm in males and oocytes in females) and to stimulate the
production of gonadal hormones such as the sex steroids.

- Glycoprotein hormone
- In females, inhibin is produced in the ovary by granulosa cells
- The corpus luteum also produces inhibin
- Inhibin is secreted into the peripheral circulation
- Affects FSH secretion (feedback actions on the reproductive axis.
Negative feedback actions on FSH secretion by direct actions at the
anterior pituitary)
- Also involves actimines
- Is of two types: inhibin A and inhibin B (same alpha subunit, but
different beta subunits)

Regulation of hormones in the reproductive axis:

1) Hypothalamus- pituitary axis (


1. Understand the processes involved in production of spermatozoa
2. Understand the processes involved in production and maturation of
Mitosis: Cell Replication

Normal cell division

Mitosis is the nuclear division in all non-gamete cells in which the
number of chromosomes is maintained (from n to n)
- Involves Interphase, prophase, metaphase, anaphase, telophase.
- Involves Making gametes
- Gamete (sperm/ova) formation involves meiosis
- Meiosis is the nuclear division in the gonads in which the number of
chromosomes is halved (from 2n to n)
- Two consecutive cell divisions (meiosis I and II) following one round of
DNA replication
- When fertilization occurs, the normal diploid chromosomal number is
restored (in human , 2n = 46)
- Produces four daughter cells
- Introduces genetic variation through random alignment (muddles up
chromosomes from two different parents) and crossover (swapping of
chromosomal sections)


Occurs in the seminiferous tubules

Produces sperm
Starts to occur at approximately 14 years of age
Results in 400 million new sperm per day
Continues throughout adult life Each mature sperm takes about 10
weeks (64 days) to make

Spermatogonia are stem cells.

- Mitosis produces a stem cell (type A) and a future sperm (type B)
- Meiosis I occurs: Primary spermatocyte (2n) two secondary
spermatocytes (n)
- Meiosis II occurs Each secondary spermatocyte (n) two spermatids
Spermatid are small nonmotile cells close to the lumen of the tubule
- Spermatids lose excess cytoplasm and form a tail, becoming
spermatozoa (sperm)


Describe the steps involved in fertilisation

- At the time of ovulation, the ovum is arrested at the metaphase (M
phase in cell cycle) 2nd meiotic division.

Meiosis I is completed by one oocyte each month

Calcium release at fertilisation this helps in the completion of the 2nd
meiotic division, only when sperm penetrates.
The steps involved are:
1. Sperm weave through granulosa cells
2. Sperm bind to zona pellucida, causing increased calcium levels in
the sperm this leads to the breakdown of membranes (acrosomal
3. Acrosomal enzymes digest holes in the zona pellucida
4. An acrosomal process is formed at the tip of the sperm, allowing it to
bind to receptors on the egg
5. The sperm and oocyte membranes fuse, releasing sperm DNA into
6. Entry of sperm contents causes increased calcium level in egg. This
triggers the cortical reaction which destroys sperm receptors and
hardens the zona pellucida.
This blocks polyspermy (egg dies from too much DNA)
Twins are split embryos or two eggs.

Polar bodies will usually undergo apoptosis in about 17 to 24 hours after

the egg forms (the final stages of telophase II (cytokinesis)) because they
have relatively little cytoplasm and shunted organelle development.
Embryonic Development: Zygote to blastocyst
- As soon as the oocyte is fertilised, it becomes a zygote
- The zygote undergoes continuous division (2 cells, 4 cells, 8cells etc)
This occurs in the absence of growth
- Once the collection of cells exceeds 16 = morula
- The cells of the morula continue to divide. A fluid filled cavity forms
and the the zona pelludica (outside layer) starts to break down forming
the blastocyst.
- The blastocyst consists of an inner cell mass, fluid filled cavity and a
layer of trophoblast cells.
This is followed by implantation:
- The zygote/morula/blastocyst is free floating and travels down the
fallopian tube and into the uterus Nourished by glycogen within
- Implantation of the blastocyst occurs about 6-7 days after fertilisation
- Integrins on the trophoblast cells allow the blastocyst to attach to
receptors in the endometrium
- If the endometrium is not mature, the blastocyst detaches and floats to
a lower level of the uterus tries to implant again
Trophoblast adheres to site in the endometrium with mature receptors and
chemical signals
Trophoblasts proliferate and form 2 layers
1. Cytotrophoblast: inner layer of cells
2. Syncytiotrophoblast: cells in the outer layer lose their plasma
membranes, invade and digest the endometrium
Further digestion occurs until the blastocyst has buried itself in the rich
endometrial environment. Endometrial cells cover blastocyst forming seal

If the implantation is successful:

- Maturation takes 6-7 days and successful implantation takes another 5
days (usually complete by the 12th day after ovulation)
- The embryo signals to the corpus luteum to continue to produce
progesterone and estrogen prevents menstruation This signalling
occurs via the human chorionic gonadotropin (hCG) hormone
- hCG levels are present in the mothers blood one week after
fertilisation and continue to rise until the end of the second month
- Measurement of hCG levels in urine is standard pregnancy test

Describe the structure and functions of the placenta and amniotic

- The human placenta is discoid (i.e. flat, circular form; disk-shaped),
weighs ~500 grams and is heavily supplied with fetal and maternal
blood vessels
- It is a temporary organ that originates from fetal and maternal tissue
- At birth placenta becomes separated and is expelled harmlessly
despite being highly vascularised.
- Placental functions:
- * Functions to transport between mum and fetus: provides substrates
for fetal metabolism- acts as gut disposes of waste- acts as kidney.
Exchanges respiratory gases- acts as lung.
- * Partial immunological barrier (fetal genotype is foreign to mother)
- * Produces hormones important for pregnancy: progesterone, estrogens
and protein hormones (inc. hCG-human chorionic gonadotrophin)


Cushions fetus from trauma and provides space to exercise growing

Prevents uterus from compressing the fetus and allows normal lung
development allows symmetrical growth
Maintains constant temperature
Provides a fluid reservoir from which the fetus swallows (stimulates gut
Consists mostly of fetal urine (also lung liquid, nasal secretions, skin
cells etc) 10ml at 8wk to 1L at 32 wks

Understand hormonal control of pregnancy and maternal

Embryo signals to the corpus luteum to continue to produce
progesterone and estrogen Via hCG which is used to detect pregnancy
Lack of progesterone or estrogen signalling induces menstruation
Progesterone is then produced by placenta to maintain pregnancy

Progesterone is essential for maintenance of pregnancy- keeps uterine

muscle quiescent
Progesterone is produced by corpus luteum in 1st 50 days, then from
Loss of Progesterone action terminates pregnancy- eg Mifepristone (or
RU-486), a progesterone receptor blocker.

Medical abortion using mifepristone is the most effective method of

abortion at gestations of less than 7 weeks.

Describe the hormonal control of lactation

- Lactation can be divided into 5 stages:
- 1. Mammogenesis Development of breasts to functional state.
- 2. Lactogenesis Synthesis and secretion of milk from the breast
- 3. Galactokinesis Ejection of milk outside the breast.
- 4. Galactopoiesis Maintenance of lactation. 5. Involution
Regression and atrophy post lactation.
- 5. Involution Regression and atrophy post lactation.

What causes maternal adaptations?

Many of the maternal adaptations are driven by hormonal changes during
Human chorionic gonadotropin (hCG) Secreted by trophoblast cells, and then
placenta Prompts corpus luteum to continue secretion of progesterone and
estrogen hCG levels rise until the end of the second month, then decline as the
placenta begins to secrete progesterone and estrogen
Progesterone and estrogen increase more slowly at the start of pregnancy but
continue to increase throughout gestation
Morning sickness results during a time when the maternal organs are adapting
to the increased concentrations of circulating progesterone and estrogen.


1. Describe the stages of puberty

- Puberty is the process through which a child matures and becomes capable of
sexual reproduction
- Result in the attainment of secondary sexual characteristics and reproductive
- Interaction between GH and gonadal steroids produces growth spurt and
activation of reproduction
* Tanner Stages of puberty (Male):
Tanner I prepubertal (testic volume< 1.5ml, small penis 3cm or less usually <
Tanner II testicular volume between 1.6 and 6 ml; skin on scrotum thins, reddens
and enlarges; penis length unchanged 9-11yrs
Tanner III testicular volume between 6 and 12 ml; scrotum enlarges further; penis
begins to lengthen to about 6 cm 11-12.5 yrs
Tanner IV testicular volume between 12 and 20 ml; scrotum enlarges further and
darkens; penis increases in length to 10 cm and circumference 12.5-14 yrs
Tanner V testicular volume greater than 20 ml; adult scrotum and penis of 15 cm
in length 14+

* Tanner Stages of puberty (Female) :

Tanner I no glandular tissue: areaola follows the skin contours of the chest
(prepubertal) [typically age 10 and younger]
Tanner II Breast bud forms, with small area of surrounding glandular tissue;
areola begins to widen [10-11.5]
Tanner III breast begins to become more elevated, and extends beyond the
borders of the areola, which continues to widen but remains in contour with
surrounding breast [11.5-13]
Tanner IV increased breast size and elevation; areola and papilla form a
secondary mound projecting from the contour of the surrounding breast [13-15]
Tanner V breast reaches final adult size; areola returns to contour of the
surrounding breast, with a projecting central papilla. [15+]

2. Understand the hormonal changes that occur during puberty

Adrenarche and gonadarche
Adrenarche: activation of adrenal androgen secretion that begins in the prepubertal phase

Adrenarche precedes puberty

An endocrine developmental process whereby humans and select

nonhuman primates increase adrenal output of a series of steroids,
especially DHEA and DHEAS.
In humans serum levels of DHEAS increase at around 6-8 years of age.
This corresponds with the development and expansion of the adrenal
What triggers the onset of adrenarche is unknown
The phenotypic hallmark of adrenarche is androgen-dependent growth
of axillary and pubic hair

Pubarche: appearance of pubic hair

Gonadarche: activation of HPG axis signalling, associated with the pubertal
growth spurt and gonadal development

The activation of the ovary and testis at the end of the prepubertal
phase of development and leads to the increase in gonadal steroid
production and the completion of gametogenesis.
Gonadarche is manifest by breast development and menarche in girls,
and by testicular enlargement and virilization in boys.
It is believed that the hypothalamus is activated or released from
We do not know what does this - candidates include: Noradrenaline,
GABA, -endorphin, NMDA, Dopamine, Growth Factors, Leptin

Thelarche: appearance of breast tissue

Menarche: onset of menses

3. Understand the factors that control the timing of puberty

Primarily determined genetically (twins studies)
Most significant environmental factor - possibly explaining as much as 25% of
the variation in the timing of puberty is nutritional status in childhood.
Earlier puberty associated with
Childhood over nutrition and obesity
Underweight children often experience delayed puberty
Highlights a critcal weight theory

It is generally accepted that the decreasing age of first period and the
onset of puberty can be related to changes in the nutritional status of

GnRH Pulses Determine Puberty Prepubertal period Restraint imposed

on pulsatile GnRH release during childhood (210 years of age) FSH and
LH low Minimal to no folliculargenesis or spermatogenesis Puberty

Increase in the pulse frequency and amplitude of GnRH release Increase

in FSH and LH pulses Folliculogenesis and spermatogenesis occur

1) To understand what a transgenic mouse and how they are generated.
- Genetically modified engineered mice
- First genetically modified animal by inserting a DNA virus into an early-stage
mouse embryo
- The inserted genes were present in every adult cell
* Types of transgenic approaches:
- Knock-out: insertion of a foreign sequence to disrupt the gene to delete or
eliminate its function (homozygote)
- Knock-in: insertion of a protein encoding cDNA sequence replaces a gene with
another, instead of deleting it.

2. To appreciate how transgenic animals are used to model human