Anjanette Acosta Physiology 3 TESTOSTERONE Anjanette Acosta Physiology 3

TESTOSTERONE Primary male sex hormone produced by the Leydig cells in the testes. Androgen (stimulates the development of male accessory organs and male characteristics) Steroid Hormone- Derived from cholesterol Roles Makes reproductive organs male in utero (due to the presence of the SRY gene on Y chromosome) Stimulates sperm production (spermatogenesis) Stimulates erythropoietin Increases Anabolic Reactions -Promotes growth of bones and muscles Increases hair growth Increases sex drive (libido)

Production of Testosterone When testosterone is low, Hypothalamus releases GnRH (Gonadotropin-Releasing Hormone) every 60-90 minutes in pulses to stimulate release of Luteinizing Hormone and Follicle Stimulating Hormone from pituitary gland into bloodstream. LH binds to LH receptors on Leydig cells in testes. Binding Starts Production: Cholesterol  Pregnenolone  Progesterone  Androstenedione  Testosterone Testosterone is then secreted by Leydig cells to be sent to target tissues.

Steroid Hormone- Derived from Cholesterol Cholesterol  Pregnenolone  Progesterone  Androstenedione  Testosterone

From Cholesterol to Pregnenolone, there are 2 Pathways to form Testosterone: In Smooth ER of Leydig Cells Pregnenolone to Progesterone Progesterone to 17-alpha-hydroxy-Progesterone 17-alpha-Progesterone to Androstenedione. Carbonyl group is added to Androstenedione to form Testosterone. Pregnenolone to 17-alpha-Hydroxy-Pregnenolone Carbonyl group is formed at C17 to make Dehydroepiandrosterone (DHEA) DHEA to form Androstenedione Carbonyl group added to Androstenedione to form Testosterone. Testosterone is reduced by 5-alpha-reductase to make Dihydrotestosterone.

Carrier Proteins Sex Hormone Binding Globulin (SHBG) Androgen Binding Protein Because it is hydrophobic, testosterone diffuses through the cell membrane. In plasma, 98% of testosterone is bound to protein, with 65% bound to sex hormone-binding globulin (SHBG) and 33% bound weakly to albumin. Both testosterone and 5α-DHT are metabolized mainly in the liver. Sex Hormone Binding Globulin (SHBG) Glycoprotein that binds to the two sex hormones: testosterone and estrogen Produced mostly by the liver and is released into the bloodstream. Other sites that produce SHBG include the brain, uterus, testes, and placenta. Testes-produced SHBG is called androgen-binding protein. Androgen-binding protein (ABP) Glycoprotein produced by the Sertoli cells in the seminiferous tubules of the testes that binds specifically to testosterone, dihydrotestosterone (DHT), and 17-beta-estradiol. Testosterone finds its way to an androgen receptor protein and enters the nucleus where it binds to DNA and initiates transcription.

Effects of Testosterone In some cell types, testosterone interacts directly with androgen receptors, whereas, in others, testosterone is converted by 5-alpha-reductase to dihydrotestosterone, an even more potent agonist for androgen receptor activation. Testosterone appears to be the primary androgen receptor-activating hormone in the Wolffian duct, whereas dihydrotestosterone (DHT) is the main androgenic hormone in the urogenital sinus, urogenital tubercle, and hair follicles. Hence, testosterone is responsible primarily for the development of male primary sexual characteristics Whereas dihydrotestosterone (DHT) is responsible for secondary male characteristics. In muscle and adipose tissue, testosterone binds directly to an androgen receptor. In liver, skin, hair, prostate gland, and gonadal tissue, testosterone must be converted first to dihydrotestosterone (DHT) by 5-alpha-reductase to be able to bind to androgen receptor and become active. In the bone and brain, testosterone is converted by aromatization to estradiol. Aromatization is the process of converting an androgen into an estrogen by the enzyme aromatase. Estrogen has an important role in the efferent ductules to epididymis and is responsible for initiating spermatogenesis. It also helps in bone strength, sexual maturation, and cholesterol metabolism.

Testosterone Blood Levels Male Female Age: T Level (ng/dL): 0-5 mo. 75-400 20-80 6 mos.-9 yrs. < 7-20 10-11 yrs. < 7-130 < 7-44 12-13 yrs. < 7-800 12-16 yrs. < 7-75 14 yrs. < 7-1,200 15-16 yrs. 100-1,200 17-18 yrs. 300-1,200 20-75 19+ yrs. 240-950 Avg. adult male 270-1,070 Avg. adult female 15-70 30+ yrs. -1% per year In male embryos, testosterone is secreted by Leydig cells by the seventh week of development, with peak concentrations reached in the second trimester. This early release of testosterone results in the anatomical differentiation of the male sexual organs. In childhood, testosterone concentrations are low. They increase during puberty, activating characteristic physical changes and initiating spermatogenesis.

Disorders Hypogonadism: Decreased functional activity of the gonads Primary: Abnormality/Defect with the testes Secondary: Pituitary Gland or Hypothalamus affecting testosterone production Possible Causes: Klinefelter's Syndrome (XXY syndrome), undescended testicles, mumps, injury to testicles, chemotherapy/radiation, inflammatory disease, HIV/AIDS, normal aging Possible Symptoms: Loss of body hair, muscle loss, reduced growth of penis and testicles, erectile dysfunction, osteoporosis, low or absent sex drive, infertility, fatigue High Levels of Testosterone: Inhibits release of LH and will then decrease testosterone levels. Treatment: Injections, skin patches, mouth patches, and gels

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