Our results indicate that SNPs of CASR gene A986S (rs1081725) and R990G (rs1042636) may increase the risk of PHPT, and the polymorphisms can potentially be used as important biological markers for early diagnosis of PHPT.
Gossypol, an antifertility agent, has inhibitory actions on many membrane-associated enzymes, suggesting that this agent might have a generalized effect on cell membranes. This hypothesis was examined in the present study using membranes and dispersed cells prepared from human and rat adrenal glands. Four parameters were determined: microviscosity as measured by fluorescence polarization of human adrenal microsomal-and mitochondrial-enriched membranes, adrenal steroidogenic enzymes; and cAMP and cortisol responses to ACTH.It was found that gossypol increased the polarization constants of microsomes and mitochondria in a dose-dependent manner. Of the three adrenal enzymes tested, both 3\g=b\-hydroxysteroiddehydrogenase \g=D\5-\g=D\4isomerase and 11-hydroxylase were inhibited by gossypol, but not 21\ x=r eq-\ hydroxylase. Using intact human adrenocortical cells, high doses of gossypol also inhibited the ACTH-stimulated cAMP and cortisol levels. The in vivo corticosterone response to ACTH in rats subjected to chronic gossypol treatment was also found to be reduced. These findings suggest that gossypol has multiple effects on adrenal function. Its effects on membrane microviscosity, adrenal steroidogenesis, cAMP and corticosterone responses to ACTH stimulation probably occur through a generalized membrane effect.In the 1930's and 40's outbreaks of unexplained infertility were observed in several provinces of China. Entire villages went for a decade or more without a recorded birth. The agent causing the infertility was identified as gossypol, a binapthalenic component of cottonseed oil, used by citizens of these regions as cooking oil. Since that time, nu¬ merous studies have investigated the pharmaco¬ logy and toxicology of gossypol, especially as an antifertility agent in males ( 1 ). Although the mecha¬ nism of action of gossypol remains to be deter¬ mined, recent studies indicate that gossypol alters the activity of many membrane-associated enzymes including those involved in steroidogenesis (2)(3)(4)(5)(6)(7)(8). This raised the possibility that gossypol may affect adrenocortical function via a generalized action on membrane and steroidogenesis.Previous studies in our laboratory have demon¬ strated that a decrease in membrane microviscosity results in a concomitant increase in the detectable number of membrane-associated prolactin recep¬ tors (9-10). In contradistinction, an increase in membrane microviscosity induced by incorpora¬ tion of long-chain saturated fatty acids was accom¬ panied by a decrease in the responsiveness of human adrenal cells to ACTH stimulation in vitro, thus providing a possible explanation for the hypoadrenal state observed in adrenoleukodystrophy and adrenomyeloneuropathy (11). Other studies have also correlated changes in membrane micro¬ viscosity with alterations in the functionality of hor¬ mone receptors, antigenic determinants, and mem¬ brane-associated enzymes in a wide variety of cells (12). Since gossypol is known to affect many mem¬ brane-associated enzymes, a potential site of...
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