Testosterone

Testosterone . It is an androgenic hormone , it is actually a prohormone , since in order to carry out its physiological or pharmacological action, it must be reduced to 5-alpha-dihydrotestosterone, which is the active hormone. It is a hormone typical of the male gender, which allows the development of man’s muscles with very little effort.

Women produce a much smaller amount, which also fulfills important functions in the regulation of aspects such as their mood, sexual appetite and sense of well-being.

Summary

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• 1 Chemical structure
• 2 Testosterone synthesis
• 3 Physiopharmacological actions
  • 1 Sexual actions
  • 2 Actions on the pituitary gland
  • 3 Metabolic actions
  • 4 Stimulation of erythropoiesis
  • 5Acciones antineoplásicas
• 4 levels of testosterone
• 5 Causes Testosterone Deficiency
• 6 Diagnosis of testosterone deficiency
• 7 Treatment of testosterone deficiency
  • 1 Risks associated with the use of testosterone
• 8 Fountains

chemical structure

Testosterone is an androgen , a steroid derived from cyclopentanoperhydrophenanthrene , which has 19 carbon atoms , a double bond between C4 and C5, an oxygen atom at C3, and a hydroxyl radical (OH) at C17. This structure is necessary for the maintenance of androgenic activity.

Testosterone can be aromatized in various tissues to form estradiol, such that a daily production of 50 micrograms is normal in man. The role of estradiol in men is not yet clear, but its absolute or relative excess can cause feminization. Testicular estrogens are probably produced by Leydig cells , but are also synthesized in other tissues from circulating androgens.

Testosterone synthesis

Testosterone is synthesized (manufactured) primarily (95%) in the testes and the rest in the adrenal glands . In women, testosterone is also synthesized in thecal cells of the ovary and in the placenta . Specifically, the Leydig cells of the testicle are the main responsible for synthesizing testosterone from cholesterol .

Testosterone synthesis is regulated by the pituitary gland and hypothalamus , which, depending on detected levels of testosterone in the blood, release hormones that stimulate or inhibit testosterone production. The pituitary gonadotropin LH, luteinizing hormone , is the specific regulatory hormone for testosterone production. Other hormones that influence testosterone synthesis to a lesser degree are prolactin , cortisol , insulin , insulin-like growth factor, estradiol, and inhibin .

cAMP activates acetate uptake from glucose or lipid metabolism and cholesterol synthesis in the smooth endoplasmic reticulum . Cholesterol is converted by mitochondrial enzymes to pregnenolone, which is the precursor to testosterone, via 17-alpha-pregnenolone, dihydroepiandrosterone , androstenedione , and finally testosterone.

The main function of the testicular Sertoli cells is to control spermatogenesis and their biological function is regulated by the gonadotropin FSH or follicle-stimulating hormone.

Sertoli cells also produce an androgen -transporting protein , ABP, which serves to bind testosterone in the testis and is the specific protein involved in transporting testosterone through the bloodstream.

Sertoli cells also produce testosterone in limited amounts. These cells are located in the seminiferous tubules and the testosterone produced seems to have a local action of special importance in spermatogenesis.

Physiopharmacological actions

sexual actions

Testosterone is necessary for the normal development of the external genitalia. This even during the first trimester of fetal life. If fetal androgen synthesis is insufficient, due to an inborn enzyme error or receptor defects, the genital phenotype may be female or ambiguous. They are called pseudohermaphrodites ( Morrison’s syndrome ), true hermaphrodites have an ovary and a testis.

In the prepubertal period there is a minimal secretion of testosterone. Through mechanisms not well understood, secretions of LH and FSH progressively increase at puberty . The testicular size also grows due to the action of growth hormone, the number of Leydig cells increases and the plasma concentration of testosterone also increases progressively, giving rise to sexual maturation. Summarizing, testosterone produces the following effects on the primary sexual organs :

• Promotes the growth of the scrotum, penis and sexual secretory glands .
• Increases weight and testicular growth.
• It stimulates spermatogenesis in the seminiferous tubules.
• It stimulates the maturation of the spermatid into spermatozoa.
• Testosterone completes the characteristics of semen and stimulates its definitive constitution as it passes through the epididymis and the vas deferens.
• Testosterone increases libido or sexual desire.

In addition, testosterone produces the following effects on secondary sexual characteristics:

• Increase in muscle mass (anabolic action).
• Proliferation of the sebaceous glands. The appearance of acne can be related to this effect.
• Skin thickening.
• Laryngealhypertrophy and permanent deep voice production.
• Distribution of male hair on: pubis, trunk, extremities and beard.

Testosterone has a genetically determined relationship with male pattern baldness , increased growth rate of long bones at puberty, and increased height. Closure of epiphyseal plates and connective cartilage . More aggressive behavior and greater physical and muscular vigor in men than in women. Anabolic actions are also evident in other organs and systems: liver , kidney , heart, bone marrow , etc.

Actions on the pituitary

By negative feedback, testosterone inhibits the secretion of pituitary gonadotropins . Testosterone or DHT inhibit the production of gonadotropin-releasing factors in the hypothalamus for the hypothalamic-pituitary portal system . The releasing factors (GnRH) are the ones that finally stimulate the secretion of LH and FSH in the anterior pituitary gland.

Aging is associated with a decrease in testicular function, with a drop in plasma testosterone concentration and a decrease in the number of interstitial Leydig cells after 60 years. At the same time, an increase in the plasma concentration of LH and FSH is observed, indicating the presence of testicular factors that affect testosterone production.

metabolic actions

Androgens and testosterone generally produce anabolic and mineralocorticoid-like effects:

• Increased protein synthesis.
• Increased nitrogen retention and positive N balance.
• Myotrophic action: Increased muscle mass.
• Increase in body height: Effect on long bones.
• Increased body weight.
• Sodium, chlorine and water retention: mineralocorticoid action.
• Phosphorus and potassium retention.

The anabolic actions of androgens may occasionally be useful therapeutically. The most used drugs for their anabolic activity are derivatives of 19-nor-testosterone, nandrolone , oxymetholone , methenolone and stanozolol . Its use, however, must be extremely prudent.

The myotrophic action is frequently sought by athletes, normally causing an abuse dangerous to health. The indiscriminate use of androgens can cause several dire consequences, including premature closure of the epiphyses and stunted growth in adolescents.

Due to the inhibition of the secretion of the gonadotropins FSH and LH, they can produce a decrease in spermatogenesis , testicular hypotrophy and atrophy , gynecomastia and feminization in men. These last effects are produced by an increase in the production of estrogens at the peripheral level.

stimulation of erythropoiesis

The erythropoietic effects of androgens are well known. Hemoglobin concentration is usually 1 to 2 g/dl higher in adult men than in women or children. In addition, moderate anemia is frequently seen in hypogonadotropic men. Androgens stimulate erythropoiesis through increased renal production of erythropoietin .

The erythropoietic effect of testosterone is not observed in bilaterally nephrectomized rats , nor in normal rats that previously received antibodies against erythropoietin. Due to these effects, androgens have been used for the treatment of aplastic anemias of different etiologies with varied responses.

An erythropoietic effect was also observed in patients with anemia associated with chronic renal failure (CRF) treated with androgens. The effects of testosterone on anemia in CRF are however controversial. Direct erythropoiesis-stimulating effects in bone marrow cell cultures by testosterone have now been observed. Thus, an increase in the development of the number of BFU-E and CFU-E erythroid colonies in culture plates containing testosterone has been demonstrated.

Antineoplastic actions

Testosterone has antineoplastic actions in inoperable advanced and metastatic breast carcinoma and where radiotherapy is not indicated. The mechanism of antineoplastic action is not well known, but there is a percentage of positive effects in approximately 30% of cases.

As this percentage of favorable results is lower than other hormonal treatments for breast cancer , the use of androgens should be reserved as a second-line alternative. Most carcinomas sensitive to androgen therapy have cells with specific receptors for androgens that can be detected with ligand binding techniques (binding) radioactively labeled in patients or in biopsy samples .

Breast carcinomas or their metastases that possess receptors generally respond to androgen therapy. In contrast , tumors that lack receptors generally do not respond to endocrine treatment . It has been speculated that in cases of reactivation of breast cancer metastases that had previously responded to androgen treatment, it is associated with loss of receptor protein production by neoplastic cells.

Higher-potency androgens are unacceptable in women due to virilization, and less-potent androgens such as danazol have less-than-obvious effects. Danazol is an androgenic derivative, also used for the treatment of endometriosis , fibrocystic breast disease and premenstrual tension syndrome. The effects are possibly related to antiestrogenic actions. Danazol is also used for the treatment of hereditary angioneurotic edema.

testosterone levels

Testosterone, despite being a male hormone, is also present in women, but to a lesser extent. The man has a testosterone secretion about 12-16 times higher than the woman. Testosterone levels also vary from one person to another and depending on the moments of life (childhood, adolescence and puberty , maturity, old age) . The testosterone produced by the Leydig cells is what passes into the bloodstream. Plasma Testosterone Concentration :

• In the adult from 300 to 1000 nanograms/dl.
• Before puberty the concentration is less than 20 ng/dl.
• The testosterone content in the human testis is approximately 300 ng/g of tissue.

Daily testosterone production :

• In adult men, the testicle produces between 2.5 and 11 mg/day of testosterone.
• In women, the ovaries and adrenal glands produce approximately 0.25 mg/day of testosterone.

Causes testosterone deficiency

Low testosterone can be caused by injury (for example, trauma, castration , radiation, or chemotherapy ), hormonal disorders (for example, pituitary gland tumors or disease , elevated prolactin levels ), or other diseases (for example, mumps ). Some medications, HIV / AIDS , and other genetic conditions (for example, Klinefelter syndrome , hemochromatosis , Kallmann syndrome , Prader-Willi syndrome , and myotonic dystrophy) can also result in a testosterone deficiency. However, in many cases the cause cannot be discovered.

Diagnosis of testosterone deficiency

During a physical exam, your doctor will examine the amount and distribution of body hair, the size of the mammary glands and penis, the size and consistency of the testicles and scrotum, and perform a visual field test.

Your doctor will also do blood tests to check if your testosterone level is within the normal range, which is 300 to 1,000 ng/dL (nanograms per deciliter), although this measurement can vary by laboratory. To diagnose low testosterone, you may need more than one blood test first thing in the morning (between 7 and 10 a.m.) and sometimes additional pituitary tests.

Testosterone deficiency treatment

Testosterone replacement therapy can stimulate sexual interest, erectile function and energy level, can improve mood, stimulate body hair growth, and increase bone density and muscle mass. There are several methods to restore testosterone: injections, patches, jellies , and a tablet that sticks to the gum . The best method depends on the cause of the problem, the patient’s preference and tolerance, and the cost. There are risks with long-term use of testosterone for men over the age of 50.

Risks associated with the use of testosterone

The risks associated with the use of testosterone are:

• Elevation of red blood cells.
• Interruption of breathing during sleep.
• Enlargement of the prostate or prostate cancers.
• Fluid accumulation (occurs rarely).

During treatment with testosterone, African-American men and those over 40 years of age who have relatives who have had prostate cancer, and all men over 50 years of age, should be closely observed. Men who have cancer of the mammary glands or who have or are suspected of having prostate cancer should not receive testosterone replacement therapy.