Blood levels and production rate of 17-hydroxypregnenolone in man.

A reliable radio-ligand assay has been developed for the measurement of 17-hydroxypregnenolone in human peripheral vein plasma. The mean plasma concentration of 17-hydroxypregnenolone was, in men, 1.9 mmug/ml; and in women, 3.5 mmug/ml. These means were not significantly different from each other, and the levels were the same in the follicular and luteal phases of the menstrual cycle. In women, the adrenal cortex was the source of the 17-hydroxypregnenolone; in men, 40% was produced by the testis. Since the metabolic clearance rate was about 2000 liters/24 hr production rate estimates were 4-7 mg/24 hr. The conversion of blood 17-hydroxypregnenolone to blood 17-hydroxyprogesterone and dehydroepiandrosterone was measured. This varied from 5 to 20%. Thus, in women during the follicular phase, 17-hydroxyprogesterone derived from blood 17-hydroxypregnenolone could be the major fraction of the 17-hydroxyprogesterone production rate. Blood 17-hydroxypregnenolone is a minor precursor of blood dehydroepiandrosterone.

Steroid formation and differentiation of cortical cells in tissue culture of human fetal adrenals in the presence and absence of ACTH.

Steroid secretion and ultrastructural differentiation of human fetal adrenal cortical cells were analyzed in tissue culture with and without ACTH. The unconjugated and sulfated endogenous neutral steroids were analyzed by gas-liquid chromatography and gas chromatography-mass spectrometry. A fetal pattern of neutral steroids, including high concentrations of sulfate conjugates, was found during the first five days of the cultivation. At 6 to 11 days of cultivation, a decrease was seen in concentrations of these steroids. However, when stimulated with ACTH, an increasing amount of steroids was secreted during days 6 to 11 and their pattern was transformed into the adult type with a 30-200 times higher secretion rate of cortisol. Cortical cells capable of proliferation in the culture had the ultrastructure of the permanent zone cells of the fetal adrenal or adult zona glomerulosa type. ACTH stimulation induced a differentiation of these cells into zona fasciculata type. The results suggest that ACTH is the main hormonal regulator in the genesis of the adult human adrenal cortex and that there is a factor during fetal life which inhibits the synthesis of the 3beta-hydroxysteroid dehydrogenase system.

In vivo production of steroids with central depressant actions by the ovary of the rat.

1. In addition to progesterone and 20-dihydroprogesterone, the following unconjugated steroids were isolated from ovarian tissue and ovarian venous blood of mature, non-pregnant rats: pregnenolone, 3betaOH-5alpha-pregnan-20-one, 3alphaOH-5alpha-pregnan-20-one, 20alphaOH-5alpha-pregnan-3-one and 5alpha-pregnane-3alpha, 20alpha-diol.2. Their concentration in the ovarian tissue and their secretion rates into the ovarian venous blood was of the same order of magnitude as that of progesterone.3. In the evening of the day of pro-oestrus significant increases in the ovarian contents of the following steroids were observed: progesterone, +140%; 3alphaOH-5alpha-pregnan-20-one, +320%; 20alphaOH-5alpha-pregnan-3-one, +195%; sum of pregnenolone and 3betaOH-5alpha-pregnan-20-one, +275%.4. At the same time the ovarian progeterone secretion rate was increased by 365%, that of 3alphaOH-5alpha-pregnan-20-one by 190%.5. A possible physiological role of the ovarian allopregnane derivatives as central depressant agents is discussed.

Interaction between prostaglandins and gonadotrophins in the rabbit ovary.

1. It has been suggested that prostaglandins function as feedback modulators of hormonal actions which are mediated by adenosine 3',5'-monophosphate (cyclic AMP). This hypothesis has been tested on the rabbit ovary, whose steroidogenic response to luteinizing hormone (LH) is mediated by the cyclic nucleotide.2. Prostaglandin E(1) (1-100 mug/ml) reduced the production of progesterone by rabbit ovaries incubated in the presence of a submaximal concentration of LH, but had no effect on the formation of this steroid when exogenous cyclic AMP was used as the stimulating agent. The prostaglandin was without effect on the formation of 20alpha-hydroxypregn-4-en-3-one in the presence of either LH or cyclic AMP.3. Prostaglandin E(2) (1 mug/ml) was without effect on ovarian steroidogenesis in the presence of LH.4. There was no evidence that exogenous prostaglandin E(1) was inactivated during incubation with rabbit ovaries in the presence of LH.5. Prostaglandin E-like compounds were detected in homogenates of incubated rabbit ovaries. However, concentrations of LH sufficient to stimulate steroidogenesis did not stimulate the synthesis of these compounds by the ovary in vitro, nor their release from the ovary in vivo.6. It is concluded that the prostaglandin-like compounds detected in the ovary are unlikely to play a role in the regulation of steroidogenesis. The results of this investigation do not support the hypothesis that prostaglandins function as general modulators of hormonal actions which are mediated by cyclic AMP.