We studied the distribution and regulation of aromatase activity in the adult rat brain with a sensitive in vitro assay that measures the amount of 3H2O formed during the conversion of [1 beta-3H]androstenedione to estrone. The rate of aromatase activity in the hypothalamus-preoptic area (HPOA) was linear with time up to 1 h, and with tissue concentrations up to 5 mgeq/200 microliters incubation mixture. The enzyme demonstrated a pH optimum of 7.4 and an apparent Michaelis-Menten constant (Km) of 0.04 microns. We found the greatest amount of aromatase activity in amygdala and HPOA from intact male rats. The hippocampus, midbrain tegmentum, cerebral cortex, cerebellum, and anterior pituitary all contained negligible enzymatic activity. Castration produced a significant decrease in aromatase activity in the HPOA (P less than 0.001), but not in the amygdala or cerebral cortex (P greater than 0.05). The HPOAs of male rats contained significantly greater aromatase activity than the HPOAs of female rats. In females, this enzyme activity did not change during the estrous cycle or after ovariectomy. Administration of testosterone to gonadectomized male and female rats significantly enhanced HPOA aromatase activities (P less than 0.05) to levels approximating those found in HPOA from intact males. Therefore, our results suggest that testosterone, or one of its metabolites, is a major steroidal regulator of HPOA aromatase activity in rats.
Experiments were conducted to examine the pulsatile nature of biologically active luteinizing hormone (LH) and progesterone secretion during the luteal phase of the menstrual cycle in rhesus monkeys. As the luteal phase progressed, the pulse frequency of LH release decreased dramatically from a high of one pulse every 90 min during the early luteal phase to a low of one pulse every 7-8 h during the late luteal phase. As the pulse frequency decreased, there was a corresponding increase in pulse amplitude. During the early luteal phase, progesterone secretion was not episodic and there were increments in LH that were not associated with elevations in progesterone. However, during the mid-late luteal phase, progesterone was secreted in a pulsatile fashion. During the midluteal phase (Days 6-7 post-LH surge), 67% of the LH pulses were associated with progesterone pulses, and by the late luteal phase (Days 10-11 post-LH surge), every LH pulse was accompanied by a dramatic and sustained release of progesterone. During the late luteal phase, when the LH profile was characterized by low-frequency, high-amplitude pulses, progesterone levels often rose from less than 1 ng/ml to greater than 9 ng/ml and returned to baseline within a 3-h period. Thus, a single daily progesterone determination is unlikely to be an accurate indicator of luteal function. These results suggest that the changing pattern of mean LH concentrations during the luteal phase occurs as a result of changes in frequency and amplitude of LH release. These changes in the pulsatile pattern of LH secretion appear to have profound effects on secretion of progesterone by the corpus luteum, especially during the mid-late luteal phase when the patterns of LH concentrations are correlated with those of progesterone.
Male rhesus monkey fetuses have significantly more testosterone (T) in their circulation than females on days 35--50 of gestation (P less than 0.01; n = 6 males and 6 females). However, we found no sex differences for androstenedione (delta 4). T concentrations remained significantly higher in male fetuses than in females later in gestation, e.g. days 79--84, 100--133, and 140--160. Levels of delta 4 differed between the sexes only on days 79--84, and dihydrotestosterone concentrations were significantly higher in male fetuses than in females on days 100--133 and 140--163. The fact that delta 4 concentrations were not different between the sexes at the earliest period studied (days 35--50) indicates that systemic concentrations of this hormone in the fetus probably are not important for sexual differentiation, especially of the central nervous system. Quantification of three steroids (T, delta 4, and dihydrotestosterone) in umbilical arterial and venous plasma from five male and nine female fetuses (days 35--100) revealed significant arterial/venous differences only for T in males (arterial greater than venous). These data, which suggest that fetal testes secrete T during morphological differentiation, lend credence to the hypothesis that endogenous T partially regulates sexual differentiation.
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