What is sex hormone ? Sex hormones are synthesized from cholesterol and secreted throughout a person's lifetime at different levels. Male gonads (testes) produce sperm. Female gonads (ovaries) produce egg. Fusion of egg and sperm occur via fertilization to produce a zygote. The zygote undergoes division to become an embryo, which eventually becomes a fetus.

1. MOLECULAR MECHANISM OF
SEX HORMONE ACTION
KHAN MOHAMMED ASIM
M.Sc. BIOTECHNOLOGY PART -II

2. What is sex hormone ?
• Sex hormones are synthesized from cholesterol and secreted throughout a person's lifetime
at different levels.
• Male gonads (testes) produce sperm.
• Female gonads (ovaries) produce egg.
• Fusion of egg and sperm occur via fertilization to produce a zygote.
• The zygote undergoes division to become an embryo, which eventually becomes a fetus.

3. Male sex hormone (Testosterone)
• Testosterone is essential for the process of spermatogenesis and male fertility and is also involved in the
development of male sex organs before birth, and the development of secondary sex characteristics at
puberty, such as voice deepening, and growth of facial and body hair etc.
• Testosterone belongs to a class of male hormones called androgens, which are sometimes called sex steroids
or anabolic steroids.
• Spermatogenesis occurs in the seminiferous tubules of the testis and within the seminiferous tubules
testosterone is the major androgen present.
• Only Leydig , peritubular and Sertoli cells express receptors for testosterone androgen receptor (AR) there
is no AR is expressed in germ cells of the mature testis due to that germ cells are not direct targets of
testosterone action.
• Major target of testosterone in the testis is the Sertoli cell, which surrounds and nourishes germ cells as they
mature into spermatozoa.
• Sertoli cells require much higher local levels of androgen more than 70 nM to fully support
spermatogenesis.

4. Mechanism of action Testosterone
• There is two pathway through which Testosterone acts on their target
cells.
1. Classical pathway
2. Non classical pathway
• The classical mechanism of testosterone action
• Testosterone act through the AR to regulate gene expression in, its stimulation causes the release of AR
from heat shock proteins HSP90,HSP70 in the cytoplasm of Sertoli cell.
• Liganded AR translocates from cytoplasm to the nucleus and binds to specific DNA sequences called
androgen response elements (AREs).
• Binding of the steroid to its receptor produces conformational changes that result in the formation of a
“transformed” or activated receptor that has high affinity for specific DNA-binding sites.
• Androgen Receptor (AR) bound to DNA recruits co-activators or corepressors to regulate testosterone
mediated transcription.
• This mechanism minimum 30–40 min to alter gene expression and hours to produce significant levels of
nascent proteins.

5. Mechanism of action Testosterone
• Non-classical testosterone signaling pathway in Sertoli cells
• Testosterone binds to the classical AR either localized near the plasma membrane or in the cytoplasm.
• After interaction with Testosterone and Androgen Receptor (AR) causes the phosphorylation (P) of Src
kinase, which may be bound to the plasma membrane or present in membrane-associated protein
complexes.
• The activated Src then phosphorylates the epidermal growth factor receptor (EGFR) directly or via
intermediary factors.
• EGFR activates the MAP kinase cascade likely through the Ras small G protein that causes the
phosphorylation of Raf kinases that activate MEK kinase that in turn activates ERK kinase.
• ERK activates the p90RSK kinase to phosphorylate CREB on serine 133 allowing CREB bound to cAMP
response elements (CREs) to recruit coactivators and induce gene transcription resulting in spermatogenesis.

6. Classical and Non-classicalTestosterone pathway

7. Female sex hormones (Estrogens, progesterone)
• Estrogens
• Estrogen production takes place in ovaries and Estradiol is most important major hormone produced in
ovaries by theca cells and luteinizeded granulosa .
• Estrogen is a generic term for estrus-producing compounds; the three most common naturally occurring
estrogens are: Estrone (E1), estradiol (E2), and estriol (E3).
• Estrogen hormones play an essential role in the growth and development of female secondary sexual
characteristics such as breasts, pubic and armpit hair, endometrium, and the regulation of the menstrual
cycle and reproductive system.
• Different type of classical and non-classical mechanism of estrogen
1. Direct genomic signaling classical pathway
2. Indirect genomic signaling
3. Non-genomic signaling
4. Ligand-independent signaling

8. Classical pathway direct genomic signaling
• The binding of 17β-estradiol to ERα or ERβ in the cytoplasm of target cells causes conformational changes
that enable receptor dimerization.
• Then translocation to the nucleus and binding to the estrogen response elements (EREs) located in or near
the promoters of target genes.
• Binding of the ligand to the receptor also triggers recruitment of a variety of coregulators in a complex that
alters chromatin structure and facilitates recruitment of the RNA polymerase II transcriptional machinery.
• Estrogen-ER complex acts as a transcriptional activator promoting gene expression.

9. Different mechanisms of estrogen signaling

10. Female sex hormones (Estrogens, progesterone)
• Progesterone
• Progesterone production takes place in corpus luteum of ovaries it belongs to a group of steroid hormones
called progestogens.
• Sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis and It belongs to a group of
steroid hormones called the progestogens also is the major progestogen in the body.
• The progesterone prepares the body for pregnancy in the event that the released egg is fertilized.
• Progesterone stimulates the growth of blood vessels that supply the lining of the womb (endometrium) and
stimulates glands in the endometrium to secrete nutrients that nourish the early embryo.
• Stimulates the growth of maternal breast tissue, prevents lactation, and strengthens the pelvic wall muscles
in preparation for labor.
• Different type of classical and non-classical mechanism of estrogen
1. Classical Mechanism of Progesterone Action
2. Non-Classical Mechanisms of Progesterone Action

11. Classical mechanism of action Progesterone
• Target of Progesterone female genital tract, breast, CNS, pituitary.
• Primary mechanism involves its interaction with E2-induced, intracellular progestin receptors (PRs).
• Progestin Receptor (PR) function as transcriptional factors, regulating the expression of genes and genomic
neural networks to initiate or sustain physiological response.
• PRs undergo significant conformational change upon binding by progesterone, leading to their nuclear
translocation, dimerization, and DNA binding.
• PRs interact with basal transcriptional machinery, assisted by coactivator molecules to initiate transcription.
• Phosphorylation of the coactivators also plays a crucial role in the activation of steroid receptors.

12. References
• Developmental biology by scott gilbrt
• https://www.livescience.com/38963-testosterone.html
• Pharmacology by k.d tripathi 6th edition
• http://www.histology.leeds.ac.uk/male/sertoli_cells.php
• https://en.wikipedia.org/wiki/Testosterone
• https://www.medicalnewstoday.com/articles/277177.php
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4210253/
• https://academic.oup.com/mend/article-lookup/doi/10.1210/me.2004-0486
• http://www.yourhormones.info/Hormones/Progesterone.aspx
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3355960/