Despite significant elevations in serum total and free testosterone, healthy young men do not demonstrate increased serum or semen PSA levels, or increased prostate volume in response to exogenous testosterone injections.
A B S T R A C T Previous studiesThese results support the concept that the effect of L-tryptophan on the secretion of human prolactin is mediated through its conversion to serotonin and are consistent with reported experimental observations that serotonin may participate in the reciprocal regulation of prolactin and gonadotropins.
INTRODUCTIONRecent studies on human prolactin have indicated the primary importance of hypothalamic mechanisms in the regulation of secretion of this hormone by the pituitary (1-3). A large body of experimental observations in animals and of pharmacological studies in the human has indicated the presence of catecholaminergic mechanisms in the hypothalamic regulation of prolactin secretion. In these studies we report an additional substance that can reciprocally regulate the secretion of prolactin and gonadotropins, the amino acid L-tryptophan. Effects observed with the intravenous infusion of this amino acid appear to relate to the presence of a serotonergic pathway mediating neuroendocrine regulation of prolactin secretion (4, 5) and provide an additional means of probing the human hypothalamic-pituitary axis.
Reports of estrone (E1) and dehydroepiandrosterone (DHEA) sulfatase (sulfohydrolase) activities within many human breast cancers have prompted us to undertake the identification and partial characterization of these enzyme activities within MCF-7 human breast cancer cells. Enzyme assays were performed within subcellular preparations and intact cultures by quantifying the total nonpolar 3H-labeled metabolites formed from [3H]E1 sulfate (E1S) and [3H]DHEA sulfate (DHEAS). The results have shown that the hydrolysis of each steroid sulfate is mediated by different particulate enzymes, which demonstrate optimal activity between pH 6.0-7.0. The analysis of enzyme kinetic data showed the Km values of E1S and DHEAS for their enzymes to be approximately 6.3 and 3.6 microM/L, respectively. Neither enzyme was subject to product inhibition. Androsterone sulfate and pregnenolone sulfate produced significant inhibition of E1, but not DHEA, sulfatase activity. E1S inhibited DHEA sulfatase competitively, with an approximate Ki of 11 microM, whereas DHEAS inhibited E2 sulfatase in a noncompetitive fashion, demonstrating an approximate Ki of 0.6 microM. Studies carried out with intact MCF-7 cultures using physiological concentrations of 3H-labeled E1S (2 nM) or DHEAS (1 microM) showed the accumulation of nonpolar metabolites during a 20-h incubation period. When cultures were incubated with similar concentrations of both steroid sulfates the apparent intracellular activity of E1 sulfatase was reduced by approximately 70%, whereas DHEA sulfatase activity remained unchanged. The results of these studies confirm the ability of MCF-7 cells to hydrolyze extracellular E1S and DHEAS, indicate that these reactions are mediated by different enzymes, and demonstrate that DHEAS is a potent inhibitor of MCF-7 E1 sulfatase. Circulating DHEAS, therefore, may substantially limit the ability of most postmenopausal breast cancers to use E1S as a substrate for intracellular estrogen biosynthesis.
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