Testis Functions

High concentrations of testosterone are locally required for continuing sperm production (in seminiferous tubules)

Testis

• Have FSH receptor

• May be the source of estradiol produced in the testes via aromatization of locally produced testosterone

• Synthesize and secrete a variety of active proteins including:

→ Müllerian duct inhibitory factor

→ Inhibin and Activin

Testis

• Found in the spaces between seminiferous tubules

• Produced testosterone with LH stimulation

Androgen

• Most important androgen secreted by the testis

• In men, 8 mg of testosterone is produced daily

→ 95% - produced by Leydig cells

→ 5% - produced by adrenals

Androgen

• 65 % of circulating testosterone is bound to sex hormone binding globulin (SHBG)

• SHBG is __________ in plasma by:

→ Estrogen

→ Thyroid hormone

→ Cirrhosis of liver

Androgen

• 65 % of circulating testosterone is bound to sex hormone binding globulin (SHBG)

• SHBG is __________ in plasma by:

→ Androgen

→ Growth hormone

→ Lower in Obese person

Androgen

• Organ for the major pathway for the degradation of testosterone

→ reduction of the double bond and ketone in the A ring, as is seen in other steroids with a Δ 4 -ketone configuration in the A ring

→ leads to the production of inactive substances such as androsterone and etiocholanolone that are then conjugated and excreted in the urine

Androgen

• Adrenal Androgens

• Contribute slightly to the normal maturation process supporting other androgen-dependent pubertal changes in the human, primarily development of pubic and axillary hair and bone maturation

• Can be converted by peripheral tissues to estrone in very small amounts (1–5%). The P450 aromatase enzyme responsible for this conversion is also found in the brain and is thought to play an important role in development.

Physiologic Effects

• Responsible for penile and scrotal growth

• Appearance of pubic, axillary, beard hair

• Sebaceous glands become more active

• Skin becomes thicker and oilier

• Larynx grows, vocal cords become thicker (low-pitched voice)

• Skeletal growth is stimulated, epiphyseal closure is accelerated

• Growth of prostate and seminal vesicles

• Darkening of skin, increase skin circulation

Physiologic Effects

• Stimulate and maintain sexual function in men

• Increase lean body mass

• Stimulate body hair growth and sebum secretion

• Reduction of hormone binding and other carrier proteins

▪ Increased liver synthesis of clotting factors, triglyceride lipase, α1- antitrypsin, haptoglobin and sialic acid

▪ Stimulate renal erythropoietin secretion

▪ Decrease HDL level

Physiologic Effects

• Improve sense of well-being

• Inhibit atherosclerosis

• Prolong life in rabbits

Physiologic Effects

• Converted by peripheral tissues to estrone in very small amounts (1-5%)

Synthetic Androgenic, Anabolic Steroids

• Testosterone, when administered ________ is rapidly absorbed

Synthetic Androgenic, Anabolic Steroids

• Testosterone, when administered ________ has more prolonged absorption time

Synthetic Androgenic, Anabolic Steroids

MOA

• Testosterone acts ___________ in target cells.

• In skin, prostate, seminal vesicles, and epididymis, it is converted to 5α-dihydrotestosterone by 5α-reductase.

Synthetic Androgenic, Anabolic Steroids

Physiologic Effects

• The natural androgens _________ erythrocyte production.

Synthetic Androgenic, Anabolic Steroids

Clinical Uses

• In the presence of pituitary deficiency, androgens are used rather than gonadotropin except when normal spermatogenesis is to be achieved.

Synthetic Androgenic, Anabolic Steroids

Clinical Uses

Androgen Replacement Therapy in Men

• Androgens are not added to the treatment regimen until puberty, at which time they are instituted in gradually increasing doses

• Start with _________ agents such as testosterone enanthate or cypionate

Synthetic Androgenic, Anabolic Steroids

Clinical Uses

Androgen Replacement Therapy in Men

• Potent but has short duration of action

Synthetic Androgenic, Anabolic Steroids

Clinical Uses

Androgen Replacement Therapy in Men

• Potent but has short duration of action

Synthetic Androgenic, Anabolic Steroids

Clinical Uses

Androgen Replacement Therapy in Men

• Given orally, not recommended since it cause liver tumor

Synthetic Androgenic, Anabolic Steroids

Clinical Uses

Gynecologic Disorders

Synthetic Androgenic, Anabolic Steroids

Clinical Uses

Gynecologic Disorders

• Weak androgen used in the treatment of endometriosis

Synthetic Androgenic, Anabolic Steroids

Clinical Uses

Aging

• Androgen production _______ with age in men

Synthetic Androgenic, Anabolic Steroids

Clinical Uses

Adverse Effects

• In women, dose of more than 200-300 mg per ______ can cause:

→ Hirsutism

→ Acne

→ Amenorrhea

→ Clitoral enlargement

→ Deepening of voice

Synthetic Androgenic, Anabolic Steroids

Clinical Uses

Adverse Effects

• Some of the androgenic steroids exert _____-gestational activity (in women):

→ lead to endometrial bleeding upon discontinuation

→ alter serum lipids and could conceivably increase

susceptibility to atherosclerotic disease in women.

Synthetic Androgenic, Anabolic Steroids

Clinical Uses

Adverse Effects

• Cause sodium retention and edema

Synthetic Androgenic, Anabolic Steroids

Clinical Uses

Contraindications