Repro ‫ئ‬ L1 bio

L1: Female sex hormones

Overview: Endocrine Physiology

Hypothalamus (GnRH)
& Pitutary

Luteinizing Hormone &

Follicle Stimulating Hormone

Ovaries & Testes

Reproduction

o Secreted from the hypothalamus

GnRH o Initiates secretion of LH and FSH
o Secreted from the anterior pituitary gland
LH o Triggers ovulation
o Convert the follicle into the corpus luteum
o Secreted from the anterior pituitary gland
FSH o Initiates follicular growth
o Secreted primarily from the follicles in the ovaries
o Promotes female secondary sex characteristics
o Causes the LH surge to trigger ovulation
o Thickens the endometrium
OES o Inhibits further LH and FSH secretion
o Decreases basal body temperature
o Decreases core temperature during exercise
o Decreases sweating threshold
o Secreted from the follicles in the ovaries
PRO o Increases basal body temperature

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1. Hypothalamus Releases Gonadotropin-Releasing Hormone (GNRH).

❖ This stimulates the anterior pituitary to release FSH and LH.

2. FSH Stimulates Maturation Of Primary Oocyte In An Immature Follicle.

3. Follicle Produces Estrogen.

Estrogen: (A) builds the uterine wall (the endometrium) (B) inhibits secretion of FSH.

4. High Levels Of Estrogen Further Stimulate Secretion Of LH By Anterior Pituitary.

❖ This plus FSH also causes ovulation of the secondary oocyte – leaving follicle without egg
(the corpus luteum).

5. Corpus Luteum Secretes Estrogen And Progesterone.

❖ This maintains the endometrium for 15-16 days and inhibits LH.

6. (If oocyte is not fertilized and implanted in the uterine wall) Corpus Degenerates (To
Corpus Albicans) And Stops Producing Estrogen And Progesterone.

7. Without Estrogen And Progesterone, Endometrium Breaks Down – Menstruation

Occurs.
❖ Menstruation is the sloughing off of the enlarged endometrial wall along with blood and
mucous.

8. Decrease In Progesterone And LH.

❖ Low LH causes secretion of FSH by pituitary again. The cycle repeats.

Regulation of Ovarian Hormones

❖ FSH influences follicles to ripen, which produces estrogen. Estrogen level gradually
increases in the second week of the menstrual cycle.
❖ Estrogen level is maximum 24 hrs before the LH peak.
❖ High doses of estrogen can suppress the LH release and, therefore, effective as
contraceptive.
❖ Under the influence of estrogen, uterine endometrium proliferates, glands in
endometrium are hypertrophied, ducts in mammary gland are proliferated and
progesterone receptors are synthesized.
❖ LH level peaks 16 hr before the ovulation. The surge of LH induces the ovulation.

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Classification:
❖ Natural Estrogens: Estradiol, estriol,estrone
❖ Synthetic estrogen:
• Steroidal: Ethinylestradiol,mestranol
• Non-steroidal: Diethylstilbestrol, hexestrol, dienestrol

❖ Estrone is the first known member of the sex hormones and was isolated by Adolf
Butenandt and Doisy independently in 1929 from the urine of pregnant women. A year
later, the estriol was isolated from human pregnancy urine by Marrian. Later, the
estradiol was also isolated

❖ Of all these, b-estradiol is most potent physiologically, estrone less potent and estriol is
least active.
❖ Their relative potencies are 50:5:1 respectively

Natural Estrogens
❖ Estradiol 3&17
• Principle estrogen in premenopausal women
❖ Estrone OH→3 / O→17
• Primary circulating estrogen after menopause
❖ Estriol 3&17&16
• Present in significant amounts during pregnancy, because its principal estrogen
produced by placenta.

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Biosynthesis.
❖ In nonpregnant females, estrogen is mainly synthesized in the ovary. The estrogen (as
well as the androgen) are, in part, transported by binding to a specific plasma protein
called sex steriod binding protein SBT. The amount of this protein increases in
pregnancy or estrogen therapy which results in reduced androgenic action. Curiously
enough, testosterone, a male hormone, is the precursor of estrogens.

Actions
On Sex Organs:
❖ Estrogens bring about pubertal changes in the femaleincluding growth of uterus,
fallopian tubes and vagina.
❖ It suppress the activity of FSH, and stimulate the secretion ofLH by direct action on
pituitary as well as through hypothalamus.
❖ It enhances the rhythmic contraction of the fallopian tubes and uterus and induce a
watery alkaline secretion from the cervix.

Metabolic Effects:
❖ Estrogen is important in maintaining bone mass primarialy bv retarding bone resorption.
Osteoclast pit formation is inhibitedbone matrix
❖ proteins increase such as osteonectin. osteocalcin, collagen etc.
❖ It controls the action of parathormone, hormone which intake calcium ions from bones
and teeth, thus maintaining a positive calcium balance.
❖ Cause salt and water retention edema

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Antioxidant effect:
❖ Estrogens decrease plasma LDL cholesterol while HDL and triglycerides levels are raised
atherosclerosis in premenopausal women,
❖ Blood coagulation is increased due to the formation of various clotting factors.
❖ It promotes vasodilation by induce secretion of nitric oxide synthase (NO) and PG12.
N. B:Protect against atherosclerosis in premenopausal and increased risk of
atherosclerosis in post-menopausal women

Notes.
o In certain mammalian species, estrogens may exert a ‘lipotropic effect’, i.e. tendency to
prevent accumulation of fats in the liver.
o Estrogens also have a cholesterol lowering effect ↓ and reduces plasma cholesterol level
and a fall in the level of β-lipoproteins ↓ (LDL).
o Young women are protected against myocardial infarction whereas women in menopause,
with decline in estrogenic activity are more susceptible to myocardial infarction.
o Estrogenic activity in premenopause is associated with increased HDL

Medical Uses of Estrogen

❖ Oral contraceptives ❖ Prostate Cancer
❖ Menopausal hormone therapy (Bone, ❖ Hypoestrogenism
Vagina, Heart) ❖ Wound healing

❖ Clomiphen citrate competes with estrogen for receptors in hypothalamus, thus

removing the feedback inhibition. So GnRH level is increased, with consequent high
levels of LH and FSH, which may produce follicular stimulation and ovulation. Clomiphen
is therefore used to produce ovulation in infertile females.

❖ Certain breast cancers, especially in perimenopausal women are estrogen-dependent. In

such patients, estrogen receptor antagonists (Tamoxifen) will block the estrogen
receptors, and cancer cells tend to die

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Progesterone
❖ Progesterone is the hormone of the corpus luteum, the structure which develops in the
ovary from the ruptured graafian follicle. It is also formed by the placenta, which
secretes progesterone, during the later part of pregnancy. Progesterone is also formed in
the adrenal cortex, as a precursor of both C19 and C21 corticosteroids. It is also
formed in the testes.

Metabolic Role
❖ Extensive development of the endometrium preparing the uterus for the embedding of
the embryo and for its nutrition.
❖ It causes an increase in glycogen ↑, mucin ↑ and fat ↑ in the lining epithelial cells.
❖ The hormone also suppresses ovulation and the production of pituitary luteinizing
hormone (LH).
❖ Progesterone modifies the action of estrogen on the vaginal epithelium during the
menstrual cycle, causing desquamation and basophilia of the superficial layer of cells and
leucocytic infiltration.
❖ Hormone also stimulates the mammary glands. In conjunction with estrogen,
progesterone causes development of the alveolar system of the breasts and sensitises
them for the action of lactogenic hormone.
❖ Progesterone is responsible for the rise in basal temperature ↑, which occurs during the
corpus luteum phase of the normal menstrual cycle. This is due to increase in basal
metabolic rate (BMR ↑ ).

Placental Hormones
❖ Peptide hormones Mainly two:
o Human chorionic gonadotropin hormone (hCG) and
o Chorionic somatomammotropin (CS) (also called placental lactogen).
❖ (b) Ovarian steroid hormones
• Progestins • Estrogens, chiefly Estrio

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❖ Pregnancy tests: Increased urinary excretion of HCG which occurs in

early pregnancy (as early as 10th day of gestation) forms the basis for
pregnancy tests.

A 20-year-old woman is not having menstrual cycles. Her plasma progesterone concentration is
found to be minimal. What is the explanation for the low level of progesterone?
A) LH secretion rate is elevated
B) LH secretion rate is suppressed
C) FSH secretion rate is suppressed
D) No corpus luteum is present
E) High inhibin concentration in the plasma has suppressed progesterone synthesis

Clomphine citrate acts by …………

1-blocking estrogen receptors
2-Blocking negative feedback of estrogen on hypothalamus and pituitary
3-Acting synergeticlly with estrogen
4-Inhibiting gonadotropine secretion

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