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Testosterone Hormone

By : Ibrahim Mahmoud Gehad Fathy

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Introduction :

Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles ,birds ,and other vertebrates. In mammals, testosterone is secreted primarily by the testicles of males and the ovaries of females, although small amounts are also secreted by the adrenal glands. It is the principal male sex hormone and an anabolic steroid.

On average, in adult males, levels of testosterone are about 7–8 times as great as in adult females

but, as the metabolic consumption of testosterone in males is greater, the daily production is about 20 times greater in men.

Females are also more sensitive to the hormone !

Secretion

1- From interstitial cells of Leyding between seminiferous tubules

“ about 20% of testicular mass “

Small amounts are secreted by adrenal glands

Overall Health effects :

In general, androgens promote protein synthesis and growth of those tissues with androgen receptors. Testosterone effects can be classified as anabolic and virlizing

Anabolic effects include growth of muscle mass and strength, increased bone density and strength, and stimulation of linear growth and bone maturation.

Androgenic effects include maturation of the sex organs, particularly the penis and the formation of the scrotum in the fetus, and after birth (usually at puberty) a deepening of the voice, growth of the beard and axillary hair. Many of these fall into the category of male secondary sex characteristics.

Mechanism of Action :

97% bound to protein in plasma3 % free

Two main cellular mechanism of action :

1- androgen receptor (directly or as DHT)

Free testosterone (T) is transported into the cytoplasm of target tissue cells, where it can bind to the androgen receptor, or can be reduced to 5α-dihydrotestosterone (DHT) by the cytoplasmic enzyme 5-alpha reductase. DHT binds to the same androgen receptor even more strongly than testosterone, so that its androgenic potency is about 5 times that of T. The T-receptor or DHT-receptor complex undergoes a structural change that allows it to move into the cell nucleus and bind directly to specific nucleotide sequences of the chromosomal DNA. The areas of binding are called hormone response elements (HREs), and influence transcriptional activity of certain genes, producing the androgen effects.

2nd mechanism

In tissues like :

Brain

Bones

It aromatization into stradiol “ female sex hormone “

In bone helps in ossification , union of epiphysis

In brain helps feedback signals in hypothalamus “ LH secr. “

Function : A- Sexual Function

1-During intrauterine life : secreted from genital ridge

Help in formation of male sex characters as :

Formation of penis , scrotum , seminal vesicles , prostate , male genital ducts

Suppretion of female genital organs

Influence the descent of testes into scrotum since 2nd month of pregnancy

2-early infancy : least understood , increases in first weeks then falls againhelps in brain development

3- before and at puberty :appearance of male secondary sex characters :- growth of hair over pubis , extension towards umbilicus , on face and chest , axillary , leg hair - growth of sex organs : testes , scrotum , penis , prostate - deepness of voice due to hypertrophy of larynx - male body type : narrow pelvis and wide shoulders -males sexual behavior associated with adulthood like desire to opposite sex - increase muscle strength -appearance of adam’s apple- growth of jaw , braw , chin . 4- in adults 1- spermatogenesis2- baldness : decrease hair growth at top of the head , provided genetic background

Metabolic effects

1- increases basal metabolic rate

2- anabolic to protein : increases muscle bulk and strength

3- on CHO : increases glycogenolysis and increase glucose uptake by cells

4- reduction f ca2+ and po4

5- union of epiphysis

6- stimulate erythropoiesis

Degraded by conjugation in liver to excrete in urine or in bile salts

Control :

1- Luteinizing hormone : the hormone secretion is stimulated by LH

2- GnRH : LH secretion is stimulated by “ GnRH “ from hypothalamus to the ant. Pituitary

3- _ve feedback mechanism : mainly by the testosterone on the hypothalamus and weaker effect on the ant. Pituitary

Other factors affects secretion : weight loss , zinc deficiency , aging , dominance challenge , sleep , training , licorice , antiandrogens

Abnormalities : a- hypogonadism in male

1- during fetal life : when the testes arenot functioning , none of male characteristics appear , instead female organs are formed

2- if boy loses his testes before puberty :

A state of eunichism : infantile sex organs and sex characters

Slightly tall because of slower union of epiphysis

3- if a man is castrated after puberty

- secondary sexual characters aren’t affected

-decreased sexual desire and sterility

-accessory sexual organs are gradually dysfunctioned

-FSH & LH are increased due to –ve feedback mechanism

B- adiposogenitial syndrome, Frolich’s syndrome,hypothalamic eunuchism

Hypogonadism due to genetic inability of hypothalamus to secrete normal amount of Gnrh & abnormality of feeding of center of hypothalamus leads to obesity with eunuchism

For fun facts : 1-A mother's testosterone level during pregnancy is correlated with her daughter's sex-typical behavior as an adult, and the correlation is even stronger than with the daughter's own adult testosterone level.

2-Falling in love decreases men's testosterone levels while increasing women's testosterone levels3- Fatherhood also decreases testosterone levels in men, suggesting that the resulting emotional and behavioral changes promote paternal care.4- men who produce less testosterone are more likely to be in love , married while those produce more are likely to be divorced .5-It has been found that when testosterone and endorphins in ejaculated semen meet the cervical wall after sexual intercourse, females receive a spike in testosterone, endorphin, and oxytocin levels, and males after orgasm during copulation experience an increase in endorphins and a marked increase in oxytocin levels.6-Testosterone levels play a major role in risk-taking during financial decisions.7-As testosterone affects the entire body (often by enlarging; males have bigger hearts, lungs, liver, etc.), the brain is also affected by this "sexual" differentiation” as males brains are larger and have more myelinated fibers

The "evolutionary neuroandrogenic theory“: focuses on the hormone testosterone as a factor influencing aggression and criminality and being evolutionarily beneficial during certain forms of competition. In most species, males are more aggressive than females. Castration of males usually has a pacifying effect on their aggressive behavior. In humans, males engage in crime and especially violent crime more than females.

Testosterone in the presence of a slow-growing cancer is assumed to increase its growth rate.

Medical uses :reducing infertility, correcting erectile dysfunction, correcting osteoporosis, encouraging penile enlargement, encouraging height growth, encouraging bone marrow stimulation and reversing the effects of anemia, and appetite stimulation.There are many routes of administration for testosterone. Forms of testosterone for human administration currently available include injectable (such as testosterone cypionate or testosterone enanthate in oil), oral, buccal, transdermal skin patches, transdermal creams, gels.

A number of lawsuits are currently underway against testosterone manufacturers, alleging a significantly increased rate of stroke and heart attack in elderly men who use testosterone supplements.

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Ibrahim Mahmoud Gehad Fathy