Pregnenolone

About: Pregnenolone is a research topic. Over the lifetime, 3539 publications have been published within this topic receiving 126444 citations. The topic is also known as: (3b)-3-hydroxy-Pregn-5-en-20-one & 3-Hydroxypregn-5-en-20-one.

Phorbol Ester Inhibition of Ovarian and Testicular Steroidogenesis in Vitro

Abstract: Possible influences of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) upon gonadal steroidogenesis were investigated in vitro Granulosa cells from hypophysectomized, estrogen-treated rats were cultured for 2 days in medium containing 01 microM androstenedione Follicle-stimulating hormone (FSH) treatment increased estrogen, progesterone, and 20 alpha-hydroxypregn-4-en-3-one production Concomitant TPA treatment inhibited FSH-stimulated estrogen production by up to 95% [concentration that induced 50% inhibition of steroid production (ED50), 11 ng/ml] TPA also inhibited FSH-stimulated progesterone (ED50, approximately 06 ng/ml) and 20 alpha-hydroxypregn-4-en-3-one (ED50, approximately 11 ng/ml) production N6O2'-dibutyryl cyclic adenosine 3':5'-monophosphate increased steroidogenesis; however, cotreatment with TPA blocked progestin but not estrogen production The TPA inhibition of progestin biosynthesis was accompanied by decreases in FSH-stimulated pregnenolone biosynthesis and 3 beta-hydroxysteroid dehydrogenase activity without decreasing the activity of 20 alpha-hydroxysteroid dehydrogenase In primary cultures of rat testicular cells, human chorionic gonadotropin treatment increased testosterone production 44-fold, whereas concomitant treatment with TPA inhibited testosterone production by up to 86% (ED50, 10 ng/ml) Cholera toxin and N6O2'-dibutyryl cyclic adenosine 3':5'-monophosphate also increased testosterone production, while the actions of these agents were decreased by TPA The TPA suppression of testosterone production was associated with a decrease in accumulation of 17 alpha-hydroxyprogesterone and androstenedione and an increase in progesterone production, suggesting a specific inhibition of 17 alpha-hydroxylase and 17,20-lyase activities These results demonstrate the inhibitory effects of a tumor promoter upon gonadotropin-stimulated steroidogenesis by cultured rat granulosa and Leydig cells through specific regulation of steroidogenic enzymes Additional studies may assist in further elucidation of cellular mechanisms associated with carcinogenesis and steroidogenesis

Neurogenic pain and steroid synthesis in the spinal cord.

Abstract: The spinal cord (SC) is a biosynthetic center for neurosteroids, including pregnenolone (PREG), progesterone (PROG), and 3alpha/5alpha-tetrahydroprogesterone (3alpha/5alpha-THP). In particular, an active form of cytochrome P450 sidechain cleavage (P450scc) has been localized in sensory networks of the rat SC dorsal horn (DH). P450scc is the key enzyme catalyzing the conversion of cholesterol (CHOL) into PREG, the rate-limiting step in the biosynthesis of all classes of steroids. To determine whether neurosteroidogenesis might be involved in the pivotal role played by the DH in nociception, effects of neurogenic pain provoked by sciatic nerve ligature were investigated on P450scc expression, cellular distribution, and activity in the SC. P450scc mRNA concentration was threefold higher in the DH of neuropathic rats than in controls. The nerve ligature also increased the density of P450sccpositive neuronal perykarya and fibers in the ipsilateral DH. Incubation of spinal tissue homogenates with [3H]CHOL revealed that the amount of newly synthesized [3H]PREG from [3H]CHOLwas 80% higher in the DH of neuropathic rats. Radioimmunoassays showed an increase of PREG and 3alpha/5alpha-THP concentrations in neuropathic rat DH. The upregulation of PREG and 3alpha/5alpha-THP biosynthesis might be involved in endogenous mechanisms triggered by neuropathic rats to cope with the chronic pain state. 3alpha/5alpha-THP formation from PREG can also generate PROG, which decreases sensitivity to pain and protects nerve cells against degeneration. Because apoptotic cell death has been demonstrated in the DH during neuropathic pain, activation of neurosteroidogenesis in spinal tissues might also be correlated to the neuroprotective role of steroids in the SC.

Indices of gonadal function in the human male. I. Plasma levels of unconjugated steroids and gonadotrophins under normal and pathological conditions.

Abstract: A radioimmunoassay technique for the simultaneous measurement of eight unconjugated steroids (progesterone, pregnenolone, dehydroepiandrosterone, androstenedione, testosterone, dihydrotestosterone, oestrone and oestradiol) in the peripheral plasma of human males is described. Determinations of these steroids and of immunoreactive FSH and LH were carried out on the plasma of twenty-one normal individuals and the levels were compared to those of eleven and ten males exhibiting oligospermia and azoospermia, respectively. Mean values and tolerance limits for each hormone, based on a lognormal distribution of individual values, are presented for all groups. Oligospermia was associated with a significant reduction in plasma dihydrotestosterone and testosterone levels. Azoospermic subjects also exhibited decreased dihydrotestosterone levels but a normal range of testosterone concentrations. Mean peripheral plasma levels of FSH were significantly elevated in both pathological groups and this was paralleled in the azoospermic men by increased concentrations of plasma LH.

In vitro maturation and ovulation of oocytes of the catfish, Heteropneustes fossilis (Bloch): effects of mammalian hypophyseal hormones, catfish pituitary homogenate, steroid precursors and metabolites, and gonadal and adrenocortical steroids.

Abstract: Wolf and Quimby medium and its modified chemically-defined version were found to be most suitable among the eight media tested for shortterm culture of oocytes of the catfish, Heteropneustes fossilis. The modified Wolf and Quimby was employed to evaluate the relative effectiveness of several hypophyseal and steroid hormones, as well as steroid precursors and metabolites in inducing in vitro maturation and ovulation in the catfish oocytes. With the exception of ovine luteinizing hormone (LH) which gave only a marginal response even at high dose levels, other mammalian hypophvseal hormones (FSH, TSH, LtH, STH and ACTH) and catfish pituitary homogenate were incapable of inducing oocyte maturation. Of the steroid precursors tested, pregnenolone, progesterone and their 17 α-hydroxy derivatives were slightly effective in inducing oocyte maturation at high concentrations. Steroid metabolites (pregnanediol-20 β) were ineffective. The sex steroids (testosterone, estrone, estriol and estradiol) did not induce oocyte maturation, while dehydroepiandrosterone and androstenedione gave only a nominal response even at high doses. Corticosteroids, principally hydrocortisone (F) and desoxycorticosterone (DOC) as also their acetates, were the most potent maturation-inducing agents even at low concentrations. These results strongly suggest that inasmuch as LH and catfish pituitary homogenate per se do not induce oocyte maturation in vitro, the terminal hormones which act directly on the oocytes to induce maturation and ovulation are the corticosteroids principally, DOC and F. The significance of these findings in the hormonal control of ovulation in the catfish is discussed.