Biochemistry of sex hormones DR.

Maha Osman

Biochemistry of sex hormones

Hormones are chemical messengers that the endocrine glands

(ductless gland) produce and release into the bloodstream.

Sex hormones:

❑ steroid hormones( containing steroid nucleus)

❑ derived from cholesterol

❑ play an essential role in sexual development and

reproduction.

❑ The main glands that produce sex hormones are the adrenal

glands and the gonads(ovaries in females and testes in

males).
Biochemistry of sex hormones DR. Maha Osman

Classification of sex hormones

Male sex hormones (androgens):
❑ Weak androgens:
➢ Dehydroepiandrosterone (DHEA)
➢ Androstenedione
❑ Strong androgens:
➢ Testosterone (testosterones also present in lower
amounts in females)
➢ Dihydrotestosterone [DHT] (more powerful than
testosterone).
Female sex hormones:

❑ Progestogens

❑ Estrogens: Include Estrone (E1), Estradiol(E2), Estriol

(E3)

Estrogens
❑ Estrone (E1):
➢ produced by a postmenopausal woman.
➢ produced by fat cells, adrenal gland, ovaries.
❑ Estradiol (E2)
➢ The most powerful and common estrogen in females
➢ present in lower amount in males
➢ produced by women before menopause
➢ produced by the ovaries
❑ Estriol (E3):
➢ produced during pregnancy
➢ produced by the placenta
Biochemistry of sex hormones DR. Maha Osman

Structure of sex hormone

Progesterone Estradiol Testesrones
21C 18C 19C
- Steroid nucleus Steroid nucleus Steroid nucleus
Ketone group at C3 Aromatic A ring Ketone group at C3
Double bond between OH at C-3 Double bond between C4
C4 and C5. Methyl group (CH3) and C5.
Methyl group (CH3) at at C13 Methyl group (CH3) at C10
C10 and C13 OH at C17 and C13
Acetyl group(CH3CO) OH at C17
at C17
Biochemistry of sex hormones DR. Maha Osman
Biochemistry of sex hormones DR. Maha Osman

Site of production:

Estrogen:

❑ Ovaries (majority)

❑ Adrenal cortex glands (lesser amount)

❑ Fat cells (lesser amount)

Progesterone

❑ Ovaries (majority)

❑ Adrenal cortex glands (lesser amount)

❑ Placenta (during pregnancy).

Testosterone

❑ Leydig cells of Testes (majority)

❑ Adrenal cortex (lesser amount)

❑ Ovaries (in female)

Biochemistry of sex hormones DR. Maha Osman

Physiological Activity of Progesterone

❑ Maintenance of Pregnancy (The name progestogens are

given because of their function in maintaining a pregnancy)

❑ Ovulation (luteal phase in the second half menstrual

cycle)

❑ Prevention of spontaneous uterine contractions

Physiological Activity of estrogens

❑ Development of female sex organs

❑ Growth of secondary sex characteristics

❑ Role in ovulation (follicular phase in the first half of

menstrual cycle)

❑ Role in bone density modulation (male + female)

❑ Role in mineral, carbohydrate, protein and lipid metabolism

Physiological Activity of androgens

➢ stimulation of the secondary sex characteristics

➢ Development of the male sex organs.

➢ Spermatogenesis

➢ Androgens also have an anabolic function in Stimulating the

production of skeletal muscles and bone as well as red blood

cells
Biochemistry of sex hormones DR. Maha Osman

Recognize biosynthesis of sex

hormones
• Hypothalamo-pituitary adrenal axis

❑ At hypothalamus:

Sex hormone synthesis is controlled by the pulsatile release of

hypothalamic gonadotropin-releasing hormone (GnRH)

❑ At the pituitary gland

• GnRH stimulates the release of luteinizing hormone

(LH) and follicle-stimulating hormone (FSH) into the

general circulation

N.B. GnRH, LH,FSH are glycoprotein hormones And they are not

sex hormones
Biochemistry of sex hormones DR. Maha Osman

❑ At testes, ovaries and adrenal cortex

1) LH then binds to its target cells and increases the

expression of steroidogenic acute regulatory protein

(StAR)

2) StAR promotes the transfer of cholesterol to the inner

mitochondrial membrane and initiates steroidogenesis

[This is the rate-limiting step of steroidogenesis in all tissues].

3) At the inner mitochondrial membrane, cholesterol is

converted to pregnenolone by the action of cytochrome

P450 side chain cleavage complex (P450scc).

Progestin synthesis
❑ Progesterone is synthesized from pregnenolone by action of

3β-hydroxy steroid dehydrogenase (3β-HSD)

❑ Site : in the corpus luteum cells, the placenta during

pregnancy and the adrenals

❑ Pregnanolone is the precursor of all other steroid hormones

(androgens and mineralocorticoids)

❑ Pregnanolone is a prohormone.
Biochemistry of sex hormones DR. Maha Osman

Androgen synthesis in males

❑ In Leydig cells in testes:

• LH initiates the production of pregnenolone

• Pregnenolone is then converted to DHEA in a two-step

process mediated by 17α-hydroxylase and 17,20-lyase

• Because Leydig cells express high levels of 3β-HSD

and 17β-HSD, DHEA is rapidly converted to

testosterone via the intermediate Androstenedione

N.B. FSH Direct stimulates the Sertoli cells resulting in spermatogenesis
LH Direct stimulates the interstitial Leydig cells to produce testosterone

❑ In the peripheral tissue of male:

• Testosterone is converted to :

➢ dihydrotestosterone (DHT) by 5α-reductase

➢ estradiol by aromatase

(Testosterone is a prohormone)
Biochemistry of sex hormones DR. Maha Osman

• (DHT):

➢ it is about one-tenth as abundant as testosterone,

➢ it accounts for most of testosterone’s biological action

Biochemistry of sex hormones DR. Maha Osman

Estrogen synthesis in females

❑ Glandular estrogen synthesis:
➢ occurs in the granulosa and theca cells of the ovaries
➢ Steps:
• LH initiate synthesis of pregnenolone in granulosa cells
• Pregnenolone diffuses to theca cells
• Pregnenolone is then converted to DHEA in a two-step
process mediated by 17α-hydroxylase and 17,20-lyase
• Theca cells express high levels of 3β-HSD that convert
DHEA to Androstenedione
• Most androstenedione returns to the granulosa cells and is
converted to estrone by aromatase, which is then converted
to estradiol by 17β-HSD
• The expression of aromatase and 17β-HSD is controlled by
FSH stimulation
N.B. The products of hormone synthesis vary with the
menstrual cycle; estradiol is the main product during follicular
maturation, whereas progesterone is the main product in the
luteal phase following ovulation

❑ Extraglandular synthesis:
• Aromatase is expressed in non-gonadal sites and facilitates
peripheral aromatization of androgens to estrone.
• Includes:
• Fat cells: increases serum estrogens by converting
androgen to estrone.
• Bone: converts testosterone to local estrogen to help
mature the epiphyses.
Biochemistry of sex hormones DR. Maha Osman

Molecular mechanism of sex hormones

Non-genomic rapid pathways are much quicker than genomic

pathways, which are slow and result in changes in the

transcription levels of specific proteins in the cell.

1) Genomic slow effects

❑ Steroid hormones ( like sex hormones) are small

hydrophobic(lipid soluble) molecules that are transported in

blood bound to serum globulin( sex steroid binding globulin).

❑ In target cell , they can cross cell membrane freely to bind

to receptor proteins in cytoplasm and/or nucleus.

Biochemistry of sex hormones DR. Maha Osman

❑ The hormone-receptor complex enter into nucleus ( if it is

formed in cytoplasm) and bind to specific DNA sequence

called response element

❑ Response elements are located in the promotor of genes

The hormone-receptor complex act as a transcription factors

which turn on (sometimes turn off) expression of genes

❑ Gene expression produce response of the cell