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.

The neurosteroid progesterone increases the expression of myelin proteins (mbp and cnpase) in rat oligodendrocytes in primary culture

Abstract: Steroid hormones are known to act in the central nervous system (CNS), affecting brain development and behavior. They have profound influences on the growth, maturation, differentiation and functioning of brain cells. The biological effects of these steroids are mediated by specific high-affinity intracellular receptors, and their presence in the brain has been described by several groups (for review see McEwen et al., 1982). In earlier studies, we have shown that newborn rat glial cells in primary culture can synthesize pregnenolone and progesterone (P) and that these brain cells contain 4 classes of steroid hormone receptors, progesterone, glucocorticoid, estrogen and androgen receptors (PR, GR, ER and AR). After treating glial cells with estrogen, only the PR was induced, and this induction was most significant in cultures established from female rat pups (Jung-Testas et al., 1991). In agreement with the presence of intracellular steroid hormone receptors, we have shown direct effects of steroids on cell multiplication, morphology and differentiation. For instance, after treatment of cells with P, an increased synthesis of myelin proteins was observed in oligodendrocytes (Jung-Testas et al., 1992). In the CNS, oligodendrocytes are responsible for myelin formation and maintenance. In rodents, central myelin is composed of about 70% lipids, among which galactocerebroside (Gal C) is a specific marker for oligodendrocytes (Raft et al., 1987), and of about 30% proteins, mainly proteolipid protein, myelin

Insulin and Insulin-Like Growth Factor-I Stimulate the 3α-Hydroxysteroid Dehydrogenase Activity of Human Placental Cytotrophoblasts*

Abstract: The placenta is the primary source of progesterone during pregnancy. Because pregnant diabetic women are reported to have higher serum progesterone levels than nondiabetic pregnant women, we studied the roles of insulin and insulin-like growth factor-I (IGF-I) in the regulation of human cytotrophoblastic 3β-hydroxysteroid dehydrogenase (3βHSD) activity. Incubation of cytotrophoblasts with insulin or IGF-I for 24 h significantly increased the ability of these cells to convert pregnenolone to progesterone by 75.8 ± 16.5% (±SE) and 65.4±12.7%, respectively. Treatment with either insulin or IGF-I did not alter cytotrophoblastic production of 20α-hydroxypregn- 4-en-3-one (the primary metabolite of progesterone), thus demonstrating that these peptides increased progesterone synthesis (i.e. 3βHSD activity) rather than decreased progesterone catabolism. Insulin and IGF-I stimulated 3βHSD activity at concentrations as low as 50 and 10 ng/ml, respectively. Insulinand IGF-I-stimulated 3βHSD activities were ...

Progesterone as a neuroactive neurosteroid, with special reference to the effect of progesterone on myelination.

Abstract: Some steroids are synthesized within the central and peripheral nervous system, mostly by glial cells. These are known as neurosteroids. In the brain, certain neurosteroids have been shown to act directly on the function of membrane receptors for neurotransmitters. For example, progesterone inhibits the neuronal nicotinic acetylcholine receptor, whereas its 3alpha,5alpha-reduced metabolite 3alpha,5alpha-tetrahydroprogesterone (allopregnanolone) activates the gamma-aminobutyric acid receptor complex A (GABA-R(A)). Besides these effects, neurosteroids also regulate important glial functions such as the synthesis of myelin proteins. Thus, in cultures of glial cells prepared from neonatal rat brain, progesterone increases the number of oligodendrocytes expressing the myelin basic protein (MBP) and the 2',3'-cyclic nucleotide-3'-phosphodiesterase (CNPase). An important role for neurosteroids in myelin repair has been demonstrated in the rodent sciatic nerve, where progesterone and its direct precursor pregnenolone are synthesized by Schwann cells. After cryolesion of the male mouse sciatic nerve, blocking the local synthesis or action of progesterone impairs remyelination of the regenerating axons, whereas administration of progesterone to the lesion site promotes the formation of new myelin sheaths.

Diazepam-binding inhibitor (DBI)-processing products, acting at the mitochondrial DBI receptor, mediate adrenocorticotropic hormone-induced steroidogenesis in rat adrenal gland.

Abstract: Diazepam-binding inhibitor (DBI) is a 9-kDa polypeptide that colocalizes in glial, adrenocortical, and Leydig cells with the mitochondrial DBI receptor (MDR). By binding with high affinity to the MDR, DBI and one of its processing products--DBI-(17-50)--regulate pregnenolone synthesis and have been suggested to participate in the immediate activation of adrenal steroidogenesis by adrenocorticotropic hormone (ACTH). In adrenals of hypophysectomized rats (1 day after surgery), ACTH failed to acutely affect the amount of adrenal DBI and the density of MDR but increased the rate of DBI processing, as determined by the HPLC profile of DBI-(17-50)-like immunoreactivity. The similar latency times for this effect and for ACTH stimulation of adrenal steroidogenesis suggest that the two processes are related. The ACTH-induced increase in both adrenal steroidogenesis and rate of DBI processing were completely inhibited by cycloheximide; this result suggests the requirement for the de novo synthesis of a protein with a short half-life, probably an endopeptidase. This enzyme, under the influence of ACTH, may activate formation of a DBI-processing product that stimulates steroidogenesis via the MDR. In support of this hypothesis is the demonstration that in hypophysectomized rats the MDR antagonist PK 11195 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxam ide completely inhibited the adrenal steroidogenesis stimulated by ACTH and by the high-affinity MDR ligand 4'-chlorodiazepam.