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Changes in adrenocortical function of the rat during the 4-day oestrous cycle and pregnancy were studied in vivo and in vitro. Regulation of adrenal production of progesterone and corticosterone was of particular interest. Morning (09.00 h) plasma concentrations of corticosterone were similar at each phase of the cycle, but a higher concentration was found in the afternoon (15.00 h pro-oestrus). However, the rate of progesterone utilization for corticosterone production by adrenal homogenates was essentially unchanged at all periods of the cycle. Therefore, the activities of the 21-and 1 1\g=b\-hydroxylatingsystems appeared not to be important determinants of plasma corticosterone levels (coefficient of determination (r2) = 0\m=.\06). These results indicate that adrenal secretion of progesterone is not specifically regulated during the cycle. On the other hand, resting plasma levels of corticosterone declined by 80\p=n-\85 % from the value on the morning of pro-oestrus between days 5 and 12 of pregnancy and then increased on day 22 and after parturition. These fluctuations did not result from alterations in the rate of metabolic clearance but rather, were closely coupled to the capacity of adrenal tissue to convert progesterone to corticosterone (r2 = 0\m=.\87). These findings suggest that progesterone utilization may be specifically curtailed at the expense of corticosterone production at days 5 and 12 of pregnancy. Concurrent measurements of adrenal venous progesterone and ovarian venous progesterone (under stressful conditions) showed that the adrenal gland secretes 2\p=n-\10times more progesterone than the ovary at all stages of the oestrous cycle, on day 22 of pregnancy, and on the first day of lactation. Thus, the adrenal gland is capable of secreting large amounts of progesterone which, if present at the appropriate time, may inhibit, delay or facilitate ovulation and onset of mating behaviour as described by other workers. Under such circumstances, however, progesterone secretion appears not to be specifically regulated but seems instead to be due to precursor spillover, since the proportionate secretion of corticosterone does not change.

The effects of prepuberal gonadectomy on adrenal function were studied in both male and female rats. Steroid production was measured in vitro using either adrenal homogenates or slices. Adrenal tissue from castrated animals of either sex produced less steroid when determined by acid fluorescence or ultraviolet absorption. The effect was reversed after replacement with testosterone or estradiol. No difference due to castration was observed when steroid production was measured with blue tetrazolium. Corticosterone added in vitro to adrenal tissue from gonadectomized rats was converted to a fluorescence negative, ultraviolet negative, blue tetrazolium positive metabolite. This conversion was inhibited by gonadal hormone replacement in. vivo. The metabolite was identified by Rf both before and after acetylation on several paper and thin layer chromatographic systems and also by infrared spectroscopy as 3/3,5o:-tetrahydrocorticosterone (compound R). Two additional compounds tentatively identified by chromatography alone were 3a,5a-tetrahydrocorticosterone and 5a-dihydrocorticosterone. Further studies showed that the decreased production of steroids by adrenal homogenates observed after ovariectomy was abolished by preincubation of the tissue as slices. Such preincubation concomitantly reduced the conversion of added corticosterone to compound R. The reaction involves 2 enzymes, 5a-reductase and 3-hydroxysteroid dehydrogenase. Activity of the latter is not increased after castration. The results demonstrate that gonadectomy enhances the capacity of the adrenal gland to convert corticosterone to compound R and other tetrahydro metabolites. The data are consistent with the hypothesis that adrenal 5a-reductase activity is increased after castration and is inhibited by replacement with testosterone or estradiol. These effects may represent a physiologic mechanism for regulation of adrenal steroid secretion. {Endo-crinology 87: 1257{Endo-crinology 87: , 1970 /CONSIDERABLE evidence is available \jk to indicate that pituitary-adrenal function is influenced by the gonadal hormones (2). However, physiologic roles for estradiol and testosterone in the regulation of adrenal function have been difficult to define. The available data seem contradictory since both stimulatory and inhibitory effects have been described for both hormones. Much of the disagreement can be related to wide variations in experimental designs used in different laboratories. For example, dose is a critical factor. The effects of estradiol and testosterone appear to