Androgen transport

Figure 25-5. Metabolism of high-density lipoprotein (HDL) in reverse cholesteroi transport. (LCAT, lecithinxholesterol acyltransferase C, cholesterol CE, cholesteryl ester PL, phospholipid A-l, apolipoprotein A-l SR-Bl, scavenger receptor B1 ABC-1, ATP binding cassette transporter 1.) Prep-HDL, HDLj, HDL3—see Table 25-1. Surplus surface constituents from the action of lipoprotein lipase on chylomicrons and VLDL are another source of preP-HDL. Hepatic lipase activity is increased by androgens and decreased by estrogens, which may account for higher concentrations of plasma HDLj in women.

Testiculat androgens are synthesized in the interstitial tissue by the Leydig cells. The immediate precursor of the gonadal steroids, as for the adrenal steroids, is cholesterol. The rate-limiting step, as in the adrenal, is delivery of cholesterol to the inner membrane of the mitochondria by the transport protein StAR. Once in the proper location, cholesterol is acted upon by the side chain cleavage enzyme P450scc. The conversion of cholesterol to pregnenolone is identical in adrenal, ovary, and testis. In the latter two tissues, however, the reaction is promoted by LH rather than ACTH. 

Isern, J., et al. Functional analysis and androgen-regulated expression of mouse organic anion transporting polypeptide 1 (Oatpl) in the kidney. Biochim. Biophys. Acta 2001, 1518, 73-78. 

Sertoli cells, in the seminiferous tubule wall, are known to be important in spermatogenesis, in part through their synthesis of an androgen-binding protein (ABP). ABP, when secreted into the lumen of the seminiferous tubules, selectively binds testosterone of Leydig cell origin and serves as a hormone reservoir and transport protein for the androgen. 

This behaviour was observed with testosteroxy-trimethylsilane (lb) in biological experiments33. The androgenic and myotropic activities of testosterone (la) and its silyl derivative lb were estimated by a routine assay (21-day-old castrated male rats s.c. injection once a day for 7 days autopsies the day after the last injection). The silyl compound lb was more active than testosterone itself. This observation may reflect rapid transport of the silicon compound across the lipid barrier and rapid cleavage to testosterone. 

Several drugs (for example amiodarone, androgens, glucocorticoids, phenytoin, and salicylates) interfere with the transport or metabolism of thyroid hormones and thereby alter thyroid function tests. These have been reviewed (90). In patients taking levothyroxine serum TSH rises after treatment with sertraline (91) and antimalarial prophylaxis with chloroquine and proguanil... 

FSH, for example, increases the expression of a polypeptide known as androgen-binding protein (ABP). ABP helps concentrate testosterone within the seminiferous tubules and helps transport testosterone to the epididymis.39 FSH may also affect Leydig cell function indirectly by increasing the production of other chemical messengers from the Sertoli cells that enhance differentiation and function of Leydig cells.146 147... 

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