Testosterone Androgens HPTA

Testosterone is the primary male sex hormone and is necessary for the maintenance of both androgenic and anabolic effects. Androgenic effects produce or stimulate the development of secondary male characteristics (masculinization) and reproduction (spermatogenesis). Anabolic effects promote or stimulate the building of tissue (bone and muscle). Serum testosterone level has a positive correlation with protein synthesis that results in increases in muscle tissue development, muscular strength, bone density, sexual desire (libido), erythropoiesis, mental cognition, and verbal fluency.

There is also a diurnal variation in circulating testosterone levels in adult men, with highest levels in the early morning, followed by a progressive fall throughout the day, to nadir levels in the evening and during the first few hours of sleep.  Frequent sampling of peripheral blood in adult men reveals small moment-to-moment fluctuations in total testosterone of 10-15%. Nadir values are approximately 15% lower than morning values, although differences of as much as 50% can occur.

The usual normal range for testosterone levels in serum samples is 300–1000 ng/dL (10–35 nM/L).  Estimate of the blood production rate of testosterone in normal adult men ranges from 5.0-7.5 mg/day.  The testosterone content of the adult human testis is only about 50 g (1 g/g testis), indicating that nearly all of the synthesized testosterone is released into the circulation.

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Androgens include what is termed the classical Anabolic Androgenic Steroid (AAS) and the recently discovered Selective Androgen Receptor Modulator (SARM). Included within this category are Performane Enhancing Drugs, which have been found to be tainted with androgens as well as designer androgens.

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The HPTA is a dynamic feedback loop.  Homeostasis is the process by which an organism maintains constant internal conditions in the face of a varying external environment. The hypothalamic pituitary testicular axis (HPTA) is the homeostatic system responsible for maintaining, supporting, and ensuring reproduction, bone density, muscle mass, and other important and vital physiological and psychological processes.

Structural components of the HPTA are the hypothalamo-pituitary, testicles, and androgen receptor (AR) located on certain end organs (prostate, bone, and muscle). The medical and scientific literature demonstrates interdependent communication must be at a certain functional level between the hypothalamo-pituitary, testes, and androgen receptor (AR) to maintain HPTA homeostasis. The major hormones of the hypothalamic pituitary testicular axis are gonadotropin releasing hormone (GnRH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), inhibin, testosterone, dihydrotestosterone (DHT), and estradiol.

In males, luteinizing hormone (LH) secretion by the pituitary positively stimulates testicular testosterone (T) production. The pulsatile secretion of gonadotropin releasing hormone (GnRH) from the hypothalamus stimulates LH secretion. Regulation of the secretion of GnRH and LH is by the negative feedback of testosterone and estradiol at the level of the hypothalamo-pituitary. Estradiol has a much larger, inhibitory effect than testosterone, being 200-fold more effective in suppressing LH secretion. 5α-reduction, DHT, does not appear to play a significant role in the negative feedback effect. Absent LH, there is no testicular testosterone production.

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