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Chapter: Modern Pharmacology with Clinical Applications: Androgens, Antiandrogens, and Anabolic Steroids

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Regulation of Plasma Testosterone

The regulation of plasma testosterone is accomplished through a dynamic feedback interaction among the hy-pothalamus, pituitary, and testis .

REGULATION OF PLASMA TESTOSTERONE

 

 

The regulation of plasma testosterone is accomplished through a dynamic feedback interaction among the hy-pothalamus, pituitary, and testis (Fig. 63.2). The hypothal-amus synthesizes and releases gonadotropin releasing hormone (GnRH) into the hypothalamic–hypophyseal portal system. Pulsatile release of GnRH stimulates the release of the pituitary gonadotropins LH and follicle-stimulating hormone (FSH). 


LH and FSH then reach the testes, where they regulate testosterone synthesis and spermatogenesis, respectively. The resultant increases in serum testosterone levels exert a negative feedback at both the hypothalamic and the pituitary levels.

 

The hypothalamus releases GnRH in a pulsatile manner. The pulse frequency is sex specific, with males exhibiting a 120-minute frequency and females exhibit-ing a 60- to 90-minute frequency. The pulsating levels of GnRH from the pituitary modulate LH and FSH re-lease. Androgens and estrogens can modulate go-nadotropin release at both the hypothalamus and pitu-itary levels. In this regard, the gonadal steroids modulate GnRH pulse frequency and amplitude at the hypothalamus level while simultaneously modifying pi-tuitary responses to GnRH by influencing GnRH re-ceptor levels in the pituitary. Increases in GnRH receptor levels with a resultant increased sensitivity to GnRH is termed up-regulation, while a decrease in GnRH re-ceptors is termed down-regulation. In the hypothala-mus, the negative feedback of testosterone involves both the conversion to dihydrotestosterone (DHT) and aromatization into estradiol.

 

A separate protein hormone produced primarily in the testis, called inhibin, also affects the secretion of FSH. Inhibin has been isolated primarily from testicular extracts but also may be found in the antral fluid of ovarian follicles in females. Inhibin decreases the re-lease of FSH from the pituitary but does not affect hy-pothalamic production of GnRH.


 

The catabolism of plasma testosterone and other androgens occurs primarily in the liver (Fig. 63.3), where they are conjugated into water-soluble com-pounds that are excreted by the kidney as the urinary 17-ketosteroids.

 

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