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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.


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Journal ArticleDOI
TL;DR: Overall, when all time points and FSH doses were analyzed collectively, FSH significantly up-regulated the mRNA expression of its own receptor and the protein level of 3β-HSD from the samples stimulated with FSH.
Abstract: STUDY QUESTION Can granulosa cells produce progesterone (P) in response to FSH stimulation? SUMMARY ANSWER FSH actively promotes P synthesis and output from granulosa cells without luteinization by up-regulating the expression and increasing enzymatic activity of 3β-hydroxysteriod dehydrogenoase (3β-HSD), which converts pregnenolone to P. WHAT IS KNOWN ALREADY Serum P level may rise prematurely prior to ovulation trigger in stimulated IVF cycles and adversely affect implantation and clinical pregnancy rates by impairing endometrial receptivity. STUDY DESIGN, SIZE, DURATION A translational research study. PARTICIPANTS/MATERIALS, SETTING, METHODS Human ovarian cortical samples (n = 15) and non-luteinizing FSH-responsive human mitotic granulosa cell line (HGrC1) were stimulated with rec-FSH at 12.5, 25 and 50 mIU/ml concentrations for 24 and 48 h. FSH receptor expression was knocked-down and up-regulated in the granulosa cells using short hairpin RNA (shRNA) technology and activin-A administration, respectively. The expressions of the steroidogenic enzymes were analyzed at mRNA level by real-time quantitative RT-PCR, and protein level by western blot and immunoprecipitation assay. The enzymatic activity of 3β-HSD was measured using a spectrophotometric method. In vitro estradiol (E2) and P productions of the cells before and after FSH stimulation were measured by electro-chemiluminescence immunoassay method. MAIN RESULTS AND THE ROLE OF CHANCE Stimulation of the HGrC1 cells with FSH resulted in a dose-dependent increase in the mRNA and protein level of 3β-HSD. Overall, when all time points and FSH doses were analyzed collectively, FSH significantly up-regulated the mRNA expression of its own receptor (3.73 ± 0.06-fold, P 0.05) did not significantly change. Similar changes were observed in the protein expression analysis of these enzymes on western blotting after FSH stimulation. FSH significantly increased 3β-HSD, 17β-HSD and aromatase in a dose-dependent manner but did not affect 17α-OH. Protein expression of P was increased along with 3β-HSD after FSH stimulation, which was further evidenced by immunoprecipitation assay. Enzymatic activity of 3β-HSD was significantly enhanced by FSH administration in the HGrC1 cells in a dose-dependent manner. In line with these findings P output (1.05 ± 0.3 vs. 0.2 ± 0.1 ng/ml, respectively, P < 0.001) from the samples stimulated with FSH were significantly increased along with E2 (1918 ± 203 vs. 932 ± 102 pg/ml, respectively, P < 0.001) compared to unstimulated controls. FSH-induced increase in 3β-HSD expression was amplified and reversed in the HGrC1 cells when FSH receptor expression was up-regulated by activin-A and down-regulated with shRNA, respectively. LIMITATIONS AND REASONS FOR CAUTION As only the effect of FSH was studied we cannot extrapolate our findings to the potential effects of HMG and recombinant LH. WIDER IMPLICATIONS OF THE FINDINGS This data provides a molecular explanation for the largely unexplained phenomenon of P rise during the follicular phase of gonadotropin stimulated IVF cycles. Our findings may progress the research to uncover potential mechanisms for preventing premature P rise that appears to be associated with inferior outcomes in women undergoing IVF. STUDY FUNDING/COMPETING INTEREST(S) Funded by the School of Medicine and the Graduate School of Health Sciences of Koc University. All authors declare no conflict of interest. TRIAL REGISTRATION NUMBER None.

71 citations

Journal ArticleDOI
TL;DR: It appeared that T is formed more readily from pregnenolone than progesterone; from 17-hydroxypregnenol one more readily than pregnanolone, progestersone or 17-Hydroxyprogest...
Abstract: Thirty-four incubations of minced testis tissue from five patients with prostatic carcinoma were performed for different periods of time with labeled precursors pregnenolone, progesterone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, dehydroepiandrosterone (DHA), androst-4-ene-3,17-dione (Δ4-dione), and androst-5-ene-3β, 17β-diol (Δ5-diol) singly or in varying combinations. Testosterone (T) and the Δ5 and Δ4 intermediates which have been suggested as possible precursors of T were identified. Metabolism of pregnenolone or 17-hydroxypregnenolone yielded steadily increasing T with a bell shaped curve depicting the Δ5 intermediates, whereas the recovery of Δ4 intermediates remained low throughout the incubation period. From a comparison of the 3H/14C ratio of intermediates with the 3H/14C ratio of T following incubations with two labeled precursors, it appeared that T is formed more readily from pregnenolone than progesterone; from 17-hydroxypregnenolone than pregnenolone, progesterone or 17-hydroxyprogest...

71 citations

Journal ArticleDOI
TL;DR: This review will focus on molecular aspects of the neurosteroid, pregnenolone sulfate, its metabolism, concentrations in serum and tissues and last not least will summarize the functional data.
Abstract: Pregnenolone sulfate is a steroid metabolite with a plethora of actions and functions. As a neurosteroid, pregnenolone sulfate modulates a variety of ion channels, transporters, and enzymes. Interestingly, as a sulfated steroid, pregnenolone sulfate is not the final- or waste-product of pregnenolone being sulfated via a phase II metabolism reaction and renally excreted, as one would presume from the pharmacology textbook knowledge. Pregnenolone sulfate is also the source and thereby the starting point for subsequent steroid synthesis pathways. Most recently, pregnenolone sulfate has been functionally "upgraded" from modulator of ion channels to an activating ion channel ligand. This review will focus on molecular aspects of the neurosteroid, pregnenolone sulfate, its metabolism, concentrations in serum and tissues and last not least will summarize the functional data.

71 citations

Journal ArticleDOI
TL;DR: Ethanol at levels commonly seen in the blood of chronic alcohol-ingesting men was shown to inhibit the activity of 17α-hydroxyprogesterone aldolase in a concentration-dependent manner, and acetaldehyde was showed to act as an inhibitor of 17 α-hydroxymethicone aldlase in the presence of androstenedione.

71 citations

Journal ArticleDOI
TL;DR: The identification of its genetic basis and the study of P450c17 enzymology have recently clarified the mechanisms by which DHEA synthesis may be regulated in adrenarche, and have suggested that the lesion underlying polycystic ovary syndrome might involve a serine kinase.
Abstract: Sex steroids, both androgens and oestrogens, are made from dehydroepiandrosterone (DHEA). The biosynthesis of DHEA from cholesterol entails four steps. First, cholesterol enters the mitochondria with the assistance of a recently described factor called the steroidogenic acute regulatory protein (StAR). Mutations in the StAR gene cause congenital lipoid adrenal hyperplasia. Next, cholesterol is converted to pregnenolone by the cholesterol side chain cleavage enzyme, P450scc. Mutations in the gene for P450scc and for its electron transfer partners, ferredoxin reductase and ferredoxin, have not been described and are probably incompatible with term gestation. Third, pregnenolone undergoes 17α-hydroxylation by microsomal P450c17. Finally, 17-OH pregnenolone is converted to DHEA by the 17,20 lyase activity of P450c17. Isolated 17,20 lyase deficiency is rare, but the identification of its genetic basis and the study of P450cl7 enzymology have recently clarified the mechanisms by which DHEA synthesis may be regulated in adrenarche, and have suggested that the lesion underlying polycystic ovary syndrome might involve a serine kinase.

71 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
202344
202255
202124
202028
201950
201835