Hormone of Reproductive System

(Synthesis and Mechanism of action )

Department of Biochemistry,
Faculty Of Medicine,
University Of Sumatera Utara
 DISCUSSION
A teenager, concerned about his weight, attempts to
maintain a fat-free diet for a period of several weeks.
If his ability to synthesize various lipids were examined,
he would be found to be most deficient in his
ability to synthesize:
A.Triacylglycerol.
B.Phospholipids.
C.Cholesterol.
D.Sphingolipids.
E.Prostaglandins.
 DISCUSSION
All of the following hormones use cyclic-AMP
as a second messenger except:
A.FSH
B.LH
C.Epinephrine
D.Glucagon
E.Estrogen
 Posterior Pituitary

Stores and releases 2 hormones that are

produced in the hypothalamus:

 ANTIDIURETIC HORMONE ADH/VASOPRESSIN):

 OXYTOCIN:
 OXYTOCIN

9 amino acid peptide,

 Produced primarily by
paraventricular nucleus and small
amount by supraoptic nucleus
Targets: Uterus and mammary
glands
 OXYTOCIN
 The term means “to stimulate birth”.
 Oxytocin acts on an estrogen-primed uterus. The
synthetic derivative of oxytocin, pitocin, is used to induce
laborcontraction of pregnant uterus
Oxytocin has an effect on the mammary glands.
Suckling generates a neurogenic reflex, which stimulates
the production of oxytocin.
It causes contraction of the myoepithelial cells expelling
the milk into milk ducts from the acini.
 Anterior Pituitary

Growth Hormone (GH)

 Thyroid Stimulating Hormone (TSH)
 Adrenocorticotropic Hormone (ACTH)
 Prolactin
 Follicle-stimulating Hormone (FSH)
 Luteinizing Hormone (LH)
 PROLACTIN

 Protein hormone of 199 amino acids.

 Secreted by lactotropic cells of adenohypophysis is under
the control of hypothalamus.
 Stimulated by TRH and vasoactive intestinal peptide.
 In females it stimulates milk production by the mammary
glands.
 Prolactin stimulates lactation on estrogen primed breast
 Release is inhibited in non-pregnant women.
 As estrogen and progesterone levels rise late in
pregnancy, it stimulates prolactin release.
 Hyperprolactinaemia can cause menstrual problems in
females In Males can cause breast enlargement
 GONADOTROPIN

 They are LH (Luteinizing hormone) and FSH

(Follicle stimulating hormone).
The placenta also produces human chorionic
gonadotropin (hCG).
 FSH and LH are secreted under the effect of
gonadotropin releasing hormone (GnRH).
HORMONAL CONTROL
OVER GONADAL FUNCTION

Estrogens
GnRH LH+FSH
Androgens

Hypothalamus Anterior pituitary Gonads -

(synthesizes (synthesizes synthesize
Gonadotropin Gonadotropins: gonadal hormones
releasing luteinizing hormone
hormone) follicle stimulating hormone)
 Action of GnRH
 A system stimulation of phosphatidylinositol is GnRH action
 GnRH binds to receptors in the cell membrane of the
gonadotrope
 Phospholipase C is activated, catalyzes the hidrolysis of PIP2
to form DAG and IP3
 DAG activates protein kinase C (PKC), which
phosphorylates specific protein
 It participate in the resulting secretory process to transport
LH and FSH to cell exterior
 IP3 stimulates of Ca2+ from calcium stroge particle, cause
increased stimulation of PKC
 participates in exocytosis of LH and FSH from cell
Action of GnRH
Follicle-stimulating hormone (FSH)
 Target: Ovaries and Testes
 In females:
• It promotes follicular growth
• Prepares the Graafian follicle for the action of LH
• Enhances the release of estrogen induced by LH.
 In males:
• It stimulates seminal tubule and testicular growth
• Plays an important role in maturation of
spermatozoa.
 Luteinizing Hormone (LH)

Target: Ovaries and Testes

Male: Production of testosterone
In females works with FSH to cause
follicle development, and then
independently is responsible for
ovulation.
 SEX/ REPRODUCTIVE HORMONES

Sex/ Reproductive hormones are elaborated by the testes, ovary and

corpus luteum mostly, and also in small quantities by the placenta and
adrenal cortex. They are all steroid compounds related to cholesterol
and are synthesised from that precursor.

Three types of reproductive hormones:

1. Estrogens or female hormones
2. Androgens or male hormones
3. Gestogens or progestational hormones.
 Ovarian hormones

 Steroids
-Estrogens
-Androgens
-Progesterone
 ESTROGEN
 Chemical structure: C18
 Source:
- follicular cells
- corpus luteum
- placenta
adrenal cortex
adipose tissue (DHEA → androstenedione )
 SYNTHESIS
 First step happens in mitochondria
 All the rest in smooth ER
 Reduction in number of carbon atoms
o Estrogens are primarily synthesized in
granulosa cells
o Androgens are primarily synthesized in
thecal cells
Synthesis of pregnenolone
Reference: Textbook of Biochemistry in students
 Estrogens in circulation
EstradiolSecreted by the ovary
EstroneDerived from peripheral
conversion of estradiol and
androstenodione
Estriol
 ESTROGENS
Transport in blood
Mostly carrier-bound (albumin, sex
hormone-binding globulin)
􀂄 Two peaks
o 􀂄 Before ovulation
o 􀂄 Mid-luteal peak
􀂄 Levels : much higher in the follicular
fluid than in the plasma!
 Mechanisms of Action
Cytoplasmic receptor binds to steroid hormone.
Translocates to nucleus.
DNA-binding domain binds to specific HRE of
the DNA.
Dimerization occurs.
 Process of 2 receptor units coming together at the 2
half-sites.
Stimulates transcription of particular genes.
Mechanisms of Action
Estrogen
Metabolism
 Metabolized to glucuronides and
sulfates
 Recycled in enterohepatic circulation
 Excreted in urine
 Testosteron

•Androgens are produced in testes (Leydig cells), adrenal cortex, ovary

and placenta. They may be formed from either (1) acetate (‘active’
acetate) or (2) cholesterol, and pregnenolone being an important
intermediate.
•Androstenedione is the immediate
precursor of testosterone.
• Testosterone is converted to more
“active” and potent form, called
“Dihydrotestosterone” (DHT) in the
testes and extratesticular tissues like
prostate, seminal vesicles and target Reference: Textbook
tissues. of Medical
Biochemistry, 8th
edition, Jaypee
Synthesis
of
testosteron

Reference: Harper’s
Illustrated
Biochemistry 31st
edition
Testosteron
 PROGESTATIONAL HORMONES
(LUTEAL HORMONES)

PROGESTERONE

Progesterone is the hormone of the corpus luteum

and 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.
it also serves as precursors for estrogens also.
 PROGESTERONE

 Progesterone is formed from

acetate via cholesterol,
‘Pregnenolone’ is the immediate
precursor.

Reference: Textbook
of Medical
Biochemistry, 8th
edition, Jaypee
Transport

 2% free
 80% albumin-bound
18% corticosteroid-binding protein
(transcortin) -bound
 OVARIAN PEPTIDE HORMONES
 Relaxin
o Relaxes pelvic joints
o Softens and dilates cervix
o Sperm mobility - in males
 Inhibin
o Selective inhibitory control of FSH
 Activin
o Selective stimulaton of FSH
o Cell differentiation
 OVARIAN PEPTIDE HORMONES
 Follistatins
o Inhibit FSH secretion
 Gonadotropin surge attenuating factor
o Prevents premature LH surge
 POMC hormones
o Vasopressin and oxytocin (in luteal
cells)
Reference

1.Textbook of Medical Biochemistry, 2012, 8th edition,

Jaypee (MN Chatterjea, Rana Shinde)
2.Harper’s Illustrated Biochemistry,2014, 31st edition
3.Lippincott’s Illustrated Reviews Biochemistry, 2011, 5th
edition
4. https://www.youtube.com/watch?v=djqqao2Uebo&t=5s
5. https://www.youtube.com/watch?v=JQcFk7J_Tf4