Testicular steroidogenesis

GnRH analogues (see Chapter 59) can induce chemical castration by suppressing the pulsatile release of LH and FSH, hence inhibiting testicular steroidogenesis. Administration of these compounds reduces circulating testosterone levels. These compounds are inhaled, injected subcutaneously, or implanted subcutaneously. They are used in males in the treatment of precocious puberty and carcinoma of the prostate. 

Maran RR. Thyroid hormones their role in testicular steroidogenesis. Arch Androl. 2003 49 375-388. 

Kleeman JM, Moore RW, Peterson RE. 1990. Inhibition of testicular steroidogenesis in... 

Regulation of Testicular Steroidogenesis Leydig-Neuroendocrine Axis... 

Wu, F.C. (1992) Testicular steroidogenesis and androgen use and abuse. Baillieres Clinical Endocrinology and Metabolism, 6, 373-403. 

Foresta, C., R. Mioni, P Bordon, F. Gottardell, A. Nogara, andM. Rossato. 1995. Erythropoietin and testicular steroidogenesis The role of second messengers. European Journal of Endocrinology 132 103-108. 

Kime, D. E., and Hyder, M., 1983, The effect of temperature and gonadotropin on testicular steroidogenesis in Sarotherodon (Tilapia) mossambicus in vitro, Gen. Comp. Endocrinol., 50 105. 

Leuprolide acetate represents a gonadotropin-releasing hormone agonist tiiat acts as a potent inhibitor of gonadotropin secretion, used as part of the treatment of prostate cancer. Continuous administration results in the suppression of ovarian and testicular steroidogenesis due to decreased levels of LH and FSH with a subsequent decrease in testosterone (male) and oestrogen (female) levels. Leuprolide may also have a direct effect on the testes by a different mechanism not directly related to reduction in serum testosterone. 

Leuprolide is a potent LH-RH agonist for the first several days to a few weeks after initiation of therapy, and therefore, it initially stimulates testicular and ovarian steroidogenesis. Because of this initial stimulation of testosterone production, it is recommended that patients with prostatic cancer be treated concurrently with leuprolide and the antiandrogen flutamide (discussed earlier). Leuprolide is generally well tolerated, with hot flashes being the most common side effect. 

The release of cholesterol from cholesterol esters occurs extra-mitochondrially by means of a cholesterol ester hydrolase in adrenals, ovaries and testicular Ley dig cells (see Ref. 6 for review). This enzyme has been studied mostly in adrenal preparations, and is known to be activated and de-activated by reversible phosphorylation [14] and that the phosphorylation was brought about by a c-AMP-dependent protein kinase [15]. Hence, ACTH stimulation of cholesterol ester activity in the adrenal occurs via the kinase and, in a similar way, trophic hormone stimulation of ovarian and testicular cholesterol ester hydrolases may occur and provide a large pool of cholesterol for steroidogenesis [16-18],... 

After hypophysectomy there is a rapid loss of LH receptors and androgen secretion by the testis. Treatment with LH alone will restore Leydig cell steroidogenesis but also causes even further decreases in testicular LH receptors. Continued treatment with LH alone leads to Leydig cell hyperplasia and an increase in LH receptors. However, even with marked Leydig cell hyperplasia in response to sustained elevations of endogenous LH, as in the tfm rat (see Ref. 6 for other references), the LH receptor content of the testis remains subnormal. 

Bartke, A., Amador, A.G., Chandrashekar Klemcke, H.G. 1987. Seasonal differences in testicular receptors and steroidogenesis. J. Steroid Biochem. 27, 581—587. 

About two-thirds of LDL is catabolized by the liver. The rest is cleared by just about all other tissues. Steroid-producing tissues are especialiy active in LDL uptake. Adrenal cells (and presumably ovarian and testicular cells) do not synthesize cholesterol at rates sufficient to support high rates of steroidogenesis. They supplement their cholesterol supply by consuming cholesterol carried on LDL and HDL. 

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