Regulation of Gonadotropin Secretion in the Male: Effect of an Aromatization Inhibitor in Estradiol-implanted, Orchidectomized Dogs

Testosterone is aromatized to estradiol in both peripheral tissues and the central nervous system. Various authors have suggested that this conversion in the male may be prerequisite for the regulation of gonadotropin secretion by testosterone. Previously, it was reported that inhibition of central nervous system aromatase caused a significant increase in plasma LH in the presence of physiologic testosterone levels (Winter et a!, 1983). In order to confirm whether aminoglutethimide, the aromatase inhibitor used in our previous study, either blocked aromatization, or the action of estradiol, the following study was conducted. Fifteen male mongrel dogs were equally divided into three groups. Group 1 dogs were implanted with estradiol-filled polydimethylsiloxane capsules only; Group 2 dogs were implanted with empty capsules and treated with 60 mg b.i.d. of aminoglutethimide; and Group 3 dogs were implanted with polydimethylsiloxane capsules filled with estradiol and treated with aminoglutethimide. Blood samples were drawn for 24 days during pretreatment, capsule implantation, castration, aminoglutethimide administration and capsule removal periods. The postcastration response of both plasma LH and FSH in dogs in groups I and 3 was suppressed in the presence of elevated estradiol, whereas that of Group 2 dogs was normal in the absence of estradiol. The results suggest that aminoglutethimide neither directly affects the plasma concentration of either LH or FSH nor blocks the effect of estradiol in inhibiting their release following castration. These data, taken together with our previous work, implicate aromatization of testosterone to estradiol in the control of gonadotropin secretion in the male

Cellular magnesium acquisition : an anomaly in embryonic cation homeostasis

Author Posting. © The Author(s), 2007. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Experimental and Molecular Pathology 83 (2007): 224-240, doi:10.1016/j.yexmp.2007.03.007.The intracellular dominance of magnesium ion makes clinical assessment difficult despite the critical role of Mg++ in many key functions of cells and enzymes. There is general consensus that serum Mg++ levels are not representative of the growing number of conditions for which magnesium is known to be important. There is no consensus method or sample source for testing for clinical purposes. High intracellular Mg++ in vertebrate embryos results in part from interactions of cations which influence cell membrane transport systems. These are functionally competent from the earliest stages, at least transiently held over from the unfertilized ovum. Kinetic studies with radiotracer cations, osmolar variations, media lacking one or more of the four biological cations, Na+, Mg++, K+, and Ca++, and metabolic poison 0.05 mEq/L NaF, demonstrated: (1) all four cations influence the behavior of the others, and (2) energy is required for uptake and efflux on different time scales, some against gradient. Na+ uptake is energy dependent against an efflux gradient. The rate of K+ loss is equal with or without fluoride, suggesting a lack of an energy requirement at these stages. Ca++ efflux took twice as long in the presence of fluoride, likely due in part to intracellular binding. Mg++ is anomalous in that early teleost vertebrate embryos have an intracellular content exceeding the surrounding sea water, an isolated unaffected yolk compartment, and a clear requirement for energy for both uptake and efflux. The physiological, pathological, and therapeutic roles of magnesium are poorly understood. This will change: (1) when 28Mg is once again generally available at a reasonable cost for both basic research and clinical assessment, and (2) when serum or plasma levels are determined simultaneously with intracellular values, preferably as part of complete four cation profiles. Atomic absorption spectrophotometry, energy-dispersive x-ray analysis, and inductively coupled plasma emission spectroscopy on sublingual mucosal and peripheral blood samples are potential methods of value for coordinated assessments.AEC Grant No. 134