Gynecology 1.6 Dr.

Tongco
Reproductive Endocrinology November 20, 2014

LEARNING OBJECTIVES
1. To learn the different hormones and different neuroendocrine
factors and their actions on different organs
2. To learn the formation and synthesis of these hormones and the
neuroendocrine factors
3. To enumerate the actions and the target organs.
4. To discuss the effect of the organ
5. To discuss the hormonal interaction in the menstrual cycle
6. To discuss folliculogenesis in relation to the menstrual cycle
 For example, one of the symptoms of polycystic ovarian syndrome
(PCOS) is hirsutism. This is due to inhibition in the formation SHBG that
results to an increase in free testosterone which induces its effect on the
hair cell follicles.
 SHBG is decreased due to hyperinsulinemia present in PCOS patients
such that [3] SHBG can be increased with exercise, pregnancy or
estrogen.
 One can give oral contraceptive pills (OCP) to manage hirsutism.

REGULATION OF REPRODUCTIVE HORMONES

REFERENCES
1. Lecture PPT
2. Recording, italicized Trigger
3. Comprehensive Gynecology 6th ed.
4. William’s obstetrics

REVIEW OF REPRODUCTIVE ENDOCRINOLOGY Cells of

Product
Origin
 Defined as the study of hormones and neuroendocrine factors that are
produced by or affect tissues like the hypothalamus, pituitary glands,
ovary, endometrium and placenta
Target
Cell
CLASSIFICATION OF FEMALE HORMONES
 BY STRUCTURE Figure 1. Regulation of Reproductive Hormones
o It could be in a series of amino acids like peptides or could be in
several benzene rings like steroids  Basically, a trigger is needed for a cell of origin to produce its hormone
o Majority of the hormones produced in the ovaries are mainly where it goes to the target cell.
steroid hormones while majority of the hormones in the pituitary  That target cell will produce a product that will give a feedback to the
gland are peptides cell of origin or to the trigger in order to increase or decrease the
production of the hormone.
Table 1. Classification of hormones based on structure
PEPTIDES STEROIDS STEROID HORMONE SYNTHESIS
o GnRH (Hypothalamus) o Estrogen (Ovaries)  Steroid hormone synthesis is a series of chemical reactions that can
o FSH, LH, Prolactin, GH, ACTH, TSH o Progesterone(Ovaries) only proceed if there's both a substrate and an enzyme
(Anterior Pituitary) o Testosterone (Ovaries)  Glands that do not have the substrate or the enzyme cannot produce
o Oxytoxin (Posterior Pituitary) the hormone
o Intraovarian peptides (there are
other hormones produced within
the ovary that affect the function Cholesterol
of the ovary) DHEA

 BY MODE OF ACTION
o Endocrine - when secreted, it travels the bloodstream and induce Progesterone Aldosterone
its effect on the target cell Cortisol
o Paracrine - when produced, it goes through its neighboring cell to
cause its effect
o Autocrine - produces a hormone which acts on itself where it
regulates its own function ADRENALS
Testosterone
 BY RECEPTORS
o Requires a receptor to guide it into the cell
o May be nuclear, cytoplasmic or through the cell membrane
o Steroid hormones act within the cell's cytoplasm while peptide
hormones act though the cell's membrane.
Estrogen
STEROID HORMONE BINDING GLOBULIN (SHBG)
 Steroid hormones are bound to sex hormone binding globulin once it is
in the bloodstream
OVARY ADIPOSE
o bound hormone - inactive
o unbound/free hormone - active Figure 2. Formation of Steroid Hormones.
(SEE APPENDIX 1 FOR PRECISE SUBSTRATE AND ENZYMES IN SYNTHESIS)
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 Basically cholesterol is the substrate needed for the production of  Cells that produce GnRH
steroid hormones.  Secretion of GnRH goes to the bloodstream and then to the
 The ovary is the main site for the production of Progesterone, hypophyseal portal vessels of the pituitary stalk
Testosterone, and Estrogen since the enzymes needed can be found in o Receives feedback from the ovaries, pituitary gland and CNS
that tissue. (cerebral cortex)
o Pulsatile secretion
 The adrenal gland needs the substrate (Progesterone) for the
 via GnRH pulse generator
production of DHEAS (Androgen), glucocorticoid (Cortisol) and  Why is this important? GnRH has to bind to a receptor in the
mineralocortioid (Aldosterone). pituitary gland which brings the molecule into the cell. If there
 Fat cells also have enzymes that can convert testosterone to estrogen is too much GnRH, the receptors in the target cells will get
which is called peripheral conversion such that in menopausal obese depleted thus, it cannot exert its function. This is called the
patients, they still have estrogen production through the fat cells. concept of DOWNREGULATION. If the secretion is not in a
 These hormones are metabolized in the liver and kidneys, which is why pulsatile fashion, it will cause downregulation of pituitary
you should not give OCT pills on a patient who has kidney or liver cells and will not secrete FSH and LH. (SEE APPENDIX 2 FOR
failure. DIAGRAM)
o Available in the market as an injection (Zoladex: Php 5-6k per
NEUROENDOCRINE FACTORS injection)
 In times of stress or strenuous exercise, there's an inhibition in the  Used to treat dysmenorrhea caused by pelvic endometriosis
production of GnRH due to an increase in Norepinephrine, Epinephrine,  To downregulate the action of GnRH on the pituitary
and endorphins, which causes a women to be ammenorrheic.  Net effect: no estrogen production, allowing the endometrial
implants to dry up
Table 1. Classification of neuroendocrine factors o Regulated by:
Neurotransmitters Neuropeptides  Estrogen
 FSH/LH
Dopamine Endorphins  GnRH
Epinephrine Enkephalins  Neurotransmitters/ neuromodulators (opioids, endorphins)
Norepinephrine Dynorphins
Serotonin
Histamine

HORMONE SOURCES AND TARGETS

 SOURCES
o Hypothalamus: GnRH
Pituitary
o Pituitary Gland: FSH, LH portal
system
o Ovary: Estrogen, Androgen, Progesterone, Intraovarian Peptide
Hormone Production
 Site of oogenesis, folliculogenesis, hormonogenesis
 TARGET TISSUES
o Uterus: proliferative to secretory endometrium in response to
hormones

MENSTRUAL CYCLE
 The interaction of the different hormones is best exemplified in the Figure 3. Hypothalamic Pituitary Portal System
menstrual cycle
 It is classified into the ovarian cycle and the endometrial cycle PRECOCIOUS PUBERTY
 The OVARIAN CYCLE is divided into:  Onset of menarche before 8 years old
o Follicular phase  Early maturation of Hypothalamic-Pituitary-Ovarian Axis.
 What is the problem here? If they secrete estrogen at an early age, the
o Luteal phase
bones will not reach their full length. There will be early epiphyseal
 The ENDOMETRIAL CYCLE is divided into:
fusion. These children will be smaller and not grow taller.
o Menstrual phase
 What do we do? Give GnRH injections continuously to temporarily stop
o Proliferative phase the axis from functioning, thus disrupting pulsatile secretion of native
o Secretory phase GnRH leading to inhibition of FSH and LH and then down the line,
estrogen.
THE HYPOTHALAMIC-PITUITARY-OVARIAN (HPO) AXIS
 GnRH agonists block the H-P-O Axis interaction and stop estrogen
THE HYPOTHALAMUS AND GnRH
synthesis
 Reproductive process starts in the brain, through the activation of the
 Prevents premature fusion of epiphysis of long bones by estrogen
initial hormonal signal that will release the gonadotropins from the
pituitary gland
STRESS
 GnRH (Gonadotropin releasing hormone)
 Can increase catecholamines which removes the pulsatile secretion of
o Main product of the hypothalamus
GnRH
o Action: stimulates release of FSH and LH from anterior pituitary
gonadotropes
o Neurosecretory cells of arcuate nucleus
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THE PITUITARY AND GONADOTROPINS  Oogenesis – oocyte development

 From anterior pituitary gonadotropes  Folliculogenesis – follicular development
 Follows pulsatile nature of GnRH  Hormonogenesis – hormone production
 Transported thru the bloodstream
 Pathway: Anterior pituitary  bloodstream  ovaries (granulosa cells) OVARIAN HORMONES
 Estrogen – from granulosa cells (stimulated by dec in FSH and inc in LH)
Table 2. FSH and LH Regulation  Progesterone – from luteinized granulosa cells (stimulated by dec in LH)
Estrogen Inhibits FSH  Androgens – from theca cells (stimulated by LH)
Stimulates LH  Intraovarian peptides
Progesterone Inhibits LH o Ex: inhibin, activin, prolactin, oocyte maturation inhibitor (OMI),
Intraovarian peptides Inhibin – inhibits FSH and LH luteinization inhibitor (LI), insulin-like growth factor (GF),
Activin – activates FSH and LH epidermal GF, interleukin-I, fibroblast GF, tumor necrosis factor
OMI
LI 2-CELL, 2-GONADOTROPIN CONCEPT OF ESTROGEN BIOSYNTHESIS
Remember!
 Negative feedback: INHIBITION
 Positive feedback: STIMULATION

What is the FSH level in menopausal women?

 There will be depletion of follicles leading to cease in estrogen
production. The pituitary gland will sense that leading to increase
secretion of FSH in order to stimulate the ovaries, but the ovaries will
not respond anymore. So if you have increased FSH, then probably you
are on the verge of menopause.

FSH (FOLLICLE STIMULATION HORMONE)

 Action on granulosa cells of ovaries to:
o Increase estrogen production
o Increase its FSH receptors
o Induce formation of LH receptors on itself – in preparation for the
second half of menstrual cycle
 Available as injection (Php 4-5k per injection)
Figure 5. 2-cell, 2-gonadotropin concept of estrogen biosynthesis. Estrogen is
produced by the granulosa cell through the stimulation of FSH, but it needs
the help of the theca cell, because the theca cell will provide the substrate
(androgen) and the enzyme in the granulosa cell will convert the substrate
Granulosa cells
Follicular fluid into estrogen. Hence, 2-cell, 2-gonadotropin concept.
- Site of FSH
action
ANTRUM **A very IMPORTANT CONCEPT, and is always asked in examinations (Dra.
Pro-oxidants Tongco)
Antioxidants
Theca cells ESTROGEN
- Site of LH  Once it is secreted, it acts on the different organs:
action o On granulosa cells: proliferation of cells and receptors for FSH, LH,
progesterone
Figure 4. Graafian Follicle o On hypothalamus/pituitary: inhibits GnRH/FSH, if there is a lot of
estrogen already
 Why do we need this? FSH action on granulosa cell causes proliferation o On endometrium: proliferation of glands
of the cell thus, more nutrients for the oocyte. This is favorable for o On cervix, fallopian tubes, breast: tissues also
women who want to get pregnant. The hormones go to the ovaries and o On corpus luteum: promotes lysis/demise
stimulate granulosa cells leading to a lot of oocyte follicular formation.  Estrogen actually has 3 forms:
This is useful for fertility treatment and for in-vitro fertilization. o Estrone (E1) – Found in abundance in a postmenopausal woman;
produced by the fat cells
LH (LUTEINIZING HORMONE) o Estradiol (E2) – Most potent and most abundant estrogen in a
 Action: woman of reproductive age
o On theca cells – low-level androgen (testosterone) production o Estriol (E3) – Found in abundance during pregnancy; synthesized in
o On mature follicles – triggers ovulation the placenta
o On granulosa cells – luteinization to convert the corpus luteum in  In menopause, FSH expected to be increased since its secretion is
the second of the cycle after the oocyte has been extruded uninhibited by the lack of estrogen production in granulosa cells. FSH
can be measured to determine if the patient is already in her
THE OVARY AND ITS HORMONES menopausal stage.
 To produce a mature ovum ready for fertilization
 To increase chance for fertilization
 To support implantation in pregnancy (through corpus luteum)
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PROGESTERONE  The luteinized granulosa cells continue to produce estrogen even in the
 Comes from the corpus luteum (luteinized granulosa and theca cells 2nd half of the ovarian cycle, but now, there is also an abundance of
from the Graafian follicle that has released its oocyte); also in the progesterone
preovulatory follicle
 Actions:
o Production of proteolytic enzymes to enhance follicular wall
rupture and ovulation
o Converts proliferative endometrium to secretory endometrium to
make it receptive for implantation
o Maintenance of pregnancy before placental development; corpus
luteum continues to secrete progesterone up to 8 weeks AOG to
support the pregnancy

FAMILY PLANNING – BASAL BODY TEMPERATURE METHOD

Figure 7. Progesterone biosynthesis

INTRAOVARIAN PEPTIDES
 Every year 1 or 2 new intraovarian peptides are being discovered
 Modulate the function within the ovary
 Function is within their name
o Inhibin – inhibits FSH
o Activin – stimulates FSH
o Prolactin
Figure 6. Basal body temperature method. Once there is a drop in o Oocyte maturation inhibitor (OMI) – prevents early maturation of
temperature, it will be followed by a rise in temperature. This rise in the oocyte, because it has to be properly timed, otherwise, it will
temperature means that ovulation has taken place and that the corpus die
luteum is there already. This is due to the thermogenic effect of o Luteinization inhibitor (LI) – premature luteinization is not good
progesterone. The drop in temperature is the most fertile period of the for the oocyte
woman. o Insulin-like GF, epidermal GF, interleukin-I, fibroblast GF, tumor
necrosis factor
ANDROGENS  Most important to remember are inhibin and activin
 Small amounts of testosterone are present in the female circulation
 Also comes from the ovary, specifically the theca cells SUMMARY OF REPRODUCTIVE HORMONES
 Once it is produced by the theca cell, it is RAPIDLY converted to estrogen Table 3. Reproductive Hormones
in the nearby granulosa cell, therefore preventing the appearance of Hypothalamus GnRH Neurosecretory cells
masculinizing symptoms of testosterone Neurotransmitters
 A block in the conversion pathway of testosterone to estrogen would Neuromodulators
cause accumulation of testosterone, resulting to the appearance of Pituitary FSH, LH Gonadotropes
masculinizing symptoms Ovary Estrogen Granulosa cells
Androgen Theca cells
POLYCYSTIC OVARIAN SYNDROME Progesterone Corpus luteum
 Syndrome of menstrual irregularity, hirsutism (commonly on the upper Intraovarian peptides Granulosa cells
lip), polycystic ovaries, and/or acne
 Due to excess androgen secretion because of hyperinsulinemia THE MENSTRUAL CYCLE
o PCOS is actually the earliest manifestation of DM ENDOMETRIAL EVENTS
o There is hyperinsulinemia due to peripheral insulin resistance  Proliferative (Follicular Phase) (0.4 – 1.0 cm)
o Insulin can mimic the action of insulin growth factor 1 (IGF-1), o Glandular proliferative mitosis
which augments androgen production by the theca cell in response o As estradiol increase with the growth and maturation of the
to LH dominant follicle, the number of estradiol receptors in the
 High androgen prevents growth of follicle, leads to premature atresia, endometrium increases and the stratum functionale proliferates
infertility, or early abortions greatly by multiplication of both glandular and stromal cells
 Midcycle (1.2 cm)
PROGESTERONE BIOSYNTHESIS IN MIDCYCLE AND LUTEAL PHASE o Appearance of subnuclear vacuoles
 Progesterone is synthesized directly from cholesterol in the luteinized  Secretory (1.2 cm)
theca cells o More vascular coiled glands, intraluminal secretions
o This correlates with a total lack of mitoses in all glands
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 Menstruation  Tranexamic acid (antifibrinolytic) aids in clot formation to reduce

o Occurs when pregnancy does not occur bleeding
o Decreasing Progesterone stimulates proteases that lead to  Progesterone is taken orally for 10-14 days to stimulate the normal
enzymatic digestion of tissues cycle and induce a withdrawal bleed to women who does not ovulate
 Shedding off of endometrium
 Blood vessels bleed GROWTH THEN ATRESIA OF OOCYTES
o Self limited event  Greatest number of oocyte is achieved 5 months of pregnancy (6 million
 Platelet plug coagulation vasoconstriction (by Pg and spiral – 7 million). At birth, only 1 million follicles will be left. At puberty
arterioles 400,000 oocytes. At menopause, it will only have 1000 up to none.
o Epithelialization because of Estrogen  There is growth then atresia (lecturer: programmed cell death; text:
tissue degeneration). All the reserves (oocytes) are going to be used up
(SEE APPENDIX 3 FOR DIAGRAM OF ENDOMETRIAL EVENTS) to ovarian atresia.
 Ovary of a Newborn will be showing many primordial follicles
ULTRASOUND APPEARANCE  Ovary Of A Woman In Reproductive Age will have lesser primordial
follicles and a lot of intravening tissue (stroma) will be seen.
 Postmenopausal Ovary will not have follicles already; it will only show
collagen/stroma.

PERIMENOPAUSE
 Cycles intially get shorter; then longer until finally amenorrheic
 Ovaries fail to secrete estrogen, FSH increases
 There is also a possibility that a woman is still in her 20’s, she will fail to
menstruate. This is called immature ovarian failure.
o This could be due low follicle supply, when depleted by surgery on
the ovary, drugs, chemotherapy, radiation, oophoritis can lead to
premature ovarian insufficiency.

FOLLICULOGENESIS

D. Midcycle phase endometrium

Figure 8. A. Proliferative phase showing thickened endometrium measuring

at 0.66cm B. Secretory phase showing thick (measuring 0.95cm) hyperechoic
endometrium with disappearnace of triple line indicating ovulation has
happened C. Post-menopausal endometrium is thinned out D. Midcycle
phase represented by a triple line indicating woman is already fertile and has
Figure 9. Diagram of folliculogenesis
a good chance of getting pregnant.
 This explains why even if women were given 6-7million oocytes,
ABNORMAL UTERINE BLEEDING
400,000 oocytes are left at puberty.
 Absence of ovulation leads to prolonged and unopposed estrogen
 The oocytes are in continuous development, the ages of primordial
stimulation of the endometrium >> lack of orderly sloughing >> heavy
follicle to primary or preantral follicle are not dependent of
and prolonged menses
gonadotropin hormones (FSH and LH). If they are not recruited to the
o No ovulation in a state of hyperestrogenism until the
menstrual cycle, these follicles just die or undergo atresia. While the
endometrium is very thick which could lead to anovulatory
rest are recruited into the menstrual cycle and are candidates for
bleeding
ovulation.
 This could lead to collapse of endometrium which could
 There can be 50-100 eggs that are undergoung folliculogenesis. But not
then lead to heavy bleeding
all make it to menstrual cycle.
 Woman who has chronic anovulation could become
malignant endometrial carcinoma due to prolonged  It’s just always growth and atresia. These who do not make it to
estrogen stimulation ovulation become scars that are also known as corpus albicans.
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ULTRASOUND OF THE OVARY
Figure 10. Ultrasound day 13. Red arrow points to a mature follicle,
this is actually 1.8-2cm, the measurement when the follicle is
mature
Figure 11. Ovary day 15. Arrow points out to “cobwebs” or air
inside. It is the follicle that transforms into a corpus luteum. This is
how the corpus luteum looks like in ultrasound.
THE OVARIAN CYCLE
(SEE APPENDIX 3 FOR DIAGRAM OF OVARIAN CYCLE EVENTS)
 The development of predictable, regular, cyclical, and spontaneous
ovulatory menstrual cycles is regulated by complex interactions of the
hypothalamic-pituitary axis, the ovaries, and the genital tract
 The ovarian-endometrial cycle has been structured as a 28-day cycle.
 The follicular phase (days 1 to 14) is characterized by rising levels of
estrogen, thickening of the endometrium, and selection of the
dominant “ovulatory” follicle.
 During the luteal phase (days 14 to 21), the corpus luteum (CL)
produces estrogen and progesterone, which prepare the endometrium
for implantation.
 If implantation occurs, the developing blastocysts will begin to produce
human chorionic gonadotropin (hCG) and rescue the corpus luteum,
thus maintaining progesterone production.
FOLLICULAR PHASE
 Follicular phase of menstrual cycle can be divided into three periods:
recruitment, selection and dominance
 Follicular phase denotes the successive recruitment of a cohort of
antral follicles, the selection of a dominant follicle, and the growth of
the selected dominant follicle[2]
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Figure 12. Follicle development: Note that progress beyond the
primary or preantral follicle stage depends on FSH stimulation.
 In the first half of the menstrual cycle, a group of follicles are recruited
into the cycle.
 Think of follicular phase as if it’s a beauty contest; recruit all the
beautiful ladies who qualify for the semi-finals. And among the chosen
semi-finalists, the winner is chosen. In other words, the proclaimed
winner here is the dominant follicle. The other follicles who fail to grow
will eventually undergo atresia (programmed cell death in the ovarian
cycle).
RECRUITMENT OF A COHORT OF ANTRAL FOLLICLES [2]
 FSH provides the critical signal for the recruitment of a cohort of
preantral follicles
 FSH signal (cyclic recruitment)
o the major survival factor that rescues the follicles from their
programmed death (atresia)
o allows follicles to start growing, increasing in size and beginning to
synthesize steroids.
 The start of each follicular phase is characterized by a small but
significant increase in the FSH:LH ratio resulting in the recruitment of a
cohort consisting of about three to seven secondary preantral follicles.
 Only preantral follicles are able to respond to the FSH signal
 Follicles at an earlier stage of development lack an independent
vascular system so that the signal does not reach them.
 Ovarian reserve is used to denote the number of antral follicles in the
ovaries and therefore to determine the capacity of the ovary to provide
oocytes that are capable of being fertilized.
o Ovarian reserve is an important tool in the treatment of infertility.
o It can be assessed by the following means:
 by a measurement of FSH on day 2 to 3 of the cycle: higher
FSH levels denote ovarian aging (resulting from a decreased
activity of the estradiol negative feedback loop), hence fewer
recruitable follicles
 by a sonographic antral follicle count
 by the measurement of inhibin B on day 2 to 3 of the cycle,
the recruitment of the follicle cohort being reflected by an
increase in this hormone produced and secreted by these
recruited follicles; thus, inhibin B levels provide an early
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 GYNECOLOGY 1.6
indicator of the number of recruited follicles and of their
secretory activity
 by the measurement of Mullerian inhibiting substance (MIS)
SELECTION OF DOMINANT FOLLICLE [2]
 Reflects the competitive advantage of the dominant follicle
 Dominant follicle is characterized by a well-vascularized theca layer
allowing a better access of the gonadotropins to their target receptors.
 This results in a greater local estradiol secretion, which in turn
increases the density of gonadotropin receptors and promotes cell
multiplication
 At the same time, elevation of peripheral estradiol levels will activate
the negative estradiol feedback loop and result in a decrease in
circulating FSH to a concentration insufficient to sustain growth in the
other follicles of the cohort.
 Because of the activiation of the negative feedback loop, the decrease
in FSH causes other follicles to stop growing.
 Granulosa cells of the recruited follicles also secrete inhibin B, the
action of which selectively suppresses FSH secretion, further decreasing
the stimulus to maturation.
 But because the dominant follicle has greater density of FSH receptors
and greater vascularization of its theca cell layer, allowing more FSH to
reach its receptors, it continues to grow
GROWTH OF THE DOMINANT FOLLICLE [2]
 GnRH pulse frequency is at its maximum (1 GnRH pulse/90 minute)
 This is the optimal pulse frequency to activate the proper gonadotropin
response to increase steroid biosynthesis and the production of
estradiol within the ovary.
 The main role of the gonadotropins and of locally produced estradiol is
to continue to stimulate growth of the dominant follicle during the
remainder of the follicular phase.
 Production of estradiol requires successive events within different
locations in the growing follicle.
 FSH receptors are located within the avascular granulosa cell layer of
the antral follicle.
o Stimulation by FSH of its receptors activates production of the
enzyme aromatase (responsible for the biosynthesis of estrogens)
within these cells.
 An important change in the structure of maturing follicles is the
acquisition of the theca cell layer, which surrounds the granulosa layer
and rapidly differentiates into the theca interna and the theca externa.
The theca layer rapidly becomes well vascularized through an active
angiogenesis process, characterized by the presence of vascular
endothelial growth factor (VEGF), which stimulates growth of new
blood vessels.
o This allows access of blood, and the hormones and nutrients it
carries, to reach the follicle and to diffuse through to the
granulosa layer.
 Circulating FSH now stimulates LH receptor synthesis within stromal
cells of the theca interna.
 LH, in turn, promotes steroid biosynthesis by theca cells and the
production of androgens.
o These androgens, following diffusion into the granulosa layer
where the enzyme aromatase is located, are then biotransformed
into estradiol.
o This leads to an overall increase in estradiol production, increased
intraovarian estradiol levels, and increased estradiol secretion into
the peripheral circulation, which parallels follicular parameter
 The dominant follicle generates its own estradiol.
 As the dominant follicle grows, an antrum (cavity) forms into which
follicular fluid accumulates.
o This fluid contains several steroids, peptide and protein hormones,
and nutrients.
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 Within the dominant follicle, the oocyte also develops and becomes
surrounded by the zona pellucida.
 This is a mucopolysaccharide coat containing specific protein sites that
later will allow only spermatozoa to penetrate and fertilize the ovum.
 Underneath the zona pellucida is the vitelline membrane that
surrounds the ooplasm.
 At the end of the follicular phase, the antral follicle contains oocytes
that are fully grown but are unable to undergo normal activation if
retrieved and fertilized in vitro.
 Activation will have to await the ovulatory LH surge.
OVULATION
 Ovulation is not just the physical release of the ovum
 The capsule of the dominant follicle should undergo changes In order
for it to break open and release the egg. Prostaglandin and proteolytic
enzymes assist in the expulsion of the oocyte (day 14)
 Ovulation (follicle rupture) occurs about 32 hours after the initial rise of
the LH surge and about 16 hours after its peak
 LH surge induces an acute inflammatory-like reaction
o Inflammatory cytokines such as interleukins, and countless genes
are up-regulated.
o There is an increase in cyclooxygenase, which catalyzes the
conversion of arachidonic acid into several prostanoids, which
include the prostaglandins that are produced intracellularly.
o Prostaglandins induce the hyperemia and edema seen in the first
hours of the process of ovulation and which result from increased
blood flow and vascular permeability. Intense protease activity is
generated in the follicle.
o The resultant proteolytic cascade, which among others involves
collagenases and plasminogen activator (which converts
plasminogen into the proteolytic enzyme plasmin), leads to the
degradation of the follicular layers and wall, which plays an
essential role in follicle rupture.
o Plasmin helps in detaching the cumulus cell-enclosed oocyte from
the granulosa cells, which initiates the process of extrusion of the
oocyte and cumulus when the follicle ruptures.
Figure 13. Diagram of LH surge during ovulation.
REMEMBER!!
 Onset: coincides with peak estrogen levels
 Onset to LH peak is 14-24 hours from the estradiol peak. Remember
that estradiol peak triggers LH surge.
 Once LH peak was attained 10-12 hours later, ovulation will happen
 Use of knowing ovulation period
o Natural family planning in a 28 day cycle, ovulation occurs on Day
14 (28-14=14)
 Cervical mucus thins out and is copious during the
preovulatory and ovulatory periods during estrogen.
 There is a lot of mucus since estrogen peaks prior to LH
secretion, thus prior to ovulation. For the ladies, increase in
mucus secretion means that you are near ovulation.
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 GYNECOLOGY 1.6

o Infertility work-up for fertilization. If there’s fertilization, fertilized egg travels from
 Follicle monitoring by ultrasound to predict when ovulation fallopian tube and goes into the uterine cavity for implantation.
will take place.
 HCG is injected to simulate LH action and trigger ovulation
 Intercourse is advised 24-36 hours from HCG injection to
increase the chance of fertilization
 LH ovulation kits may also be used wherein a positive test
would indicate LH surge happened.

LUTEAL PHASE

Figure 15. Course of oocyte right after fertilization to the events of

implantation

Note: Some of the image used in this are obtained either from the
Figure 14. After the oocyte is extruded from the mature dominant follicle, recommended text or from the internet or re-diagrammed since there was
the amount of follicular fluid is markedly reduced, the follicular wall no powerpoint provided and pictures of slides were inadequate.
becomes convoluted, and the follicular diameter and volume greatly
decrease. As a result, a new ovarian structure evolves from the ovulated
follicle, the corpus luteum.2]

 The corpus luteum is the result of two important events initiated at

ovulation.
o First, granulosa and theca cells hypertrophy, take up increasing
amounts of lipids, and acquire organelles associated with
steroidogenesis.
o Second, the basal lamina, which separated the granulosa and
theca cell layers, is disrupted, and capillaries from the theca
interna now invade the granulosa layer (which up to now had
been avascular) to form an extensive capillary network.
 The result is that each steroidogenic cell within the corpus
luteum is in close proximity to blood vessels.
 The hallmark of the human corpus luteum is its secretion primarily of
progesterone.
 Although there is a significant drop in estradiol and androgen secretion
at ovulation, 17- hydroxylase and aromatase are present in the corpus
luteum, so that it also secretes 17-hydroxyprogesterone and estradiol.
Significant amounts of inhibin A are also produced. [2]
 Corpus luteum has life span of 14 ± 2 days. If there is no pregnancy the
corpus luteum disappears.
 LH stimulates progesterone secretion
 Progesterone
o induces secretory changes in the endometrium
o prevents the development of new follicles

FERTILIZATION AND IMPLANTATION

 In case of a pregnancy, there is an ovulation, release of the oocytes,
goes into the fallopian tube where oocytes wait for the mighty sperm
for fertilization. If there’s fertilization, fertilized egg travels from
fallopian tube and goes into the uterine cavity for implantation.
 In case of a pregnancy, there is an ovulation, release of the oocytes,
goes into the fallopian tube where oocytes wait for the mighty sperm

Group 24 | Uy And, Uy Ash, Uy Je, Valera, Vallester Page 8 of 9

 Gynecology 1.6 Dr. Tongco
Endocrinology November 20, 2014

APPENDIX

Appendix 1. Formation of Steroid Hormones Appendix 2. GnRH Concept of Downregulation

Appendix 3. Diagram of gonadotropin control of the ovarian and endometrial cycles.

Group 24 | Uy And, Uy Ash, Uy Je, Valera, Vallester Page 9 of 9