This enzyme is involved in the conversion of pregnenolone to progesterone, 17 alpha-hydroxypregnenolone to 17 alpha-hydroxyprogesterone and dehydroepiandrosterone to androstenedione. It utilizes NAD+ as the cofactor. Two different human 3 beta-HSD genes have been identified and localized to chromosome 1p13.1. The type I gene is expressed primarily in the human placenta, skin and adipose tissue. The type II gene encodes the 3 beta-HSDexpressed in the gonads and adrenal cortex. The DNA sequences of the exons of the two genes are very similar such that the encoded proteins differ in only 23 amino acid residues.
General function
Enzyme, Oxidoreductase
Comment
Arif et al. (1999) reported an association between premature ovarian failure, 3betaHSD autoimmunity, and a distinctive HLA-DQ molecule and proposed the hypothesis that autoantibodies to this steroid cell enzyme may be markers of autoimmune ovarian failure.
Cellular localization
Comment
3 beta-HSD is localized to the microsomal fraction.
Martel et al. (1990) have studied the effect of chronic treatment with LH (hCG), FSH, and PRL on ovarian 3 beta-HSD expression and activity in hypophysectomized adult female rats. PRL caused a 81% decrease in ovarian 3 beta-HSD mRNA content accompanied by a similar decrease in 3 beta-HSD activity and protein levels. In situ hybridization experiments showed that the inhibitory effect of PRL is exerted primarily on luteal cell 3 beta-HSD expression and activity. On the other hand, it can be seen that hCG stimulates 3 beta-HSD mRNA accumulation in interstitial cells. McGee et al. (1995) reported that insulin alone increased 3 beta HSD protein content as measured by Western analysis 1.8-2-fold over basal levels, whereas FSH alone increased protein content 2.8-fold, and was further
augmented by the addition of insulin in a dose-related fashion up to 3.5-fold over basal levels. Insulin increased 3 beta HSD mRNA twofold over
basal levels; FSH alone increased mRNA expression of 3 beta HSD 3.2-fold. In the presence of insulin plus FSH, 3 beta HSD mRNA expression increased
7.6-fold over basal levels. Miro et al. (1995) reported that treatment in vitro with FSH alone markedly
enhanced the abundance of the 3 beta HSD mRNA transcript in
nondifferentiated and differentiated rat granulosa cells.
Gene expression increased. Luteinization of porcine preovulatory follicles leads to systematic changes in follicular gene expression. Agca C et al. The LH surge initiates the luteinization of preovulatory follicles and causes hormonal and structural changes that ultimately lead to ovulation and the formation of corpora lutea. The objective of the study was to examine gene expression in ovarian follicles (n = 11) collected from pigs (Sus scrofa domestica) approaching estrus (estrogenic preovulatory follicle; n = 6 follicles from two sows) and in ovarian follicles collected from pigs on the second day of estrus (preovulatory follicles that were luteinized but had not ovulated; n = 5 follicles from two sows). The follicular status within each follicle was confirmed by follicular fluid analyses of estradiol and progesterone ratios. Microarrays were made from expressed sequence tags that were isolated from cDNA libraries of porcine ovary. Gene expression was measured by hybridization of fluorescently labeled cDNA (preovulatory estrogenic or -luteinized) to the microarray. Microarray analyses detected 107 and 43 genes whose expression was decreased or increased (respectively) during the transition from preovulatory estrogenic to -luteinized (P<0.01). Cells within preovulatory estrogenic follicles had a gene-expression profile of proliferative and metabolically active cells that were responding to oxidative stress. Cells within preovulatory luteinized follicles had a gene-expression profile of nonproliferative and migratory cells with angiogenic properties. Approximately, 40% of the discovered genes had unknown function.
Juneau et al. (1993) reported that the first expression of the 3 beta-HSD enzyme
was observed 6 days after birth in rats, immunolabeling as well as autoradiographic reaction for mRNA being found in a few interstitial gland cells. At the 10th day of postnatal life, the theca interna cells of
growing follicles appeared to be labeled with both techniques. The granulosa cells of growing follicles also exhibited hybridization signal,
whereas no immunostaining could be detected in these cells at any of the time intervals studied. At puberty, 3 beta-HSD was localized in theca interna and granulosa cells of the growing and mature follicles as well as in the interstitial gland and corpus luteum cells.
Follicle stages
Secondary, Antral, Preovulatory, Corpus luteum
Comment
Development of Steroid Signaling Pathways during Primordial Follicle Formation in the Human Fetal Ovary. Fowler PA et al. Context: Ovarian primordial follicle formation is critical for subsequent human female fertility. It is likely that steroid, and especially estrogen, signaling is required for this process, but details of the pathways involved are currently lacking. Objective: The aim was to identify and characterize key members of the steroid-signaling pathway expressed in the second trimester human fetal ovary. Design: We conducted an observational study of the female fetus, quantifying and localizing steroid-signaling pathway members. Setting: The study was conducted at the Universities of Aberdeen, Edinburgh, and Glasgow. Patients/Participants: Ovaries were collected from 43 morphologically normal human female fetuses from women undergoing elective termination of second trimester pregnancies. Main Outcome Measures: We measured mRNA transcript levels and immunolocalized key steroidogenic enzymes and steroid receptors, including those encoded by ESR2, AR, and CYP19A1. Results: Levels of mRNA encoding the steroidogenic apparatus and steroid receptors increased across the second trimester. CYP19A1 transcript increased 4.7-fold during this period with intense immunostaining for CYP19A detected in pregranulosa cells around primordial follicles and somatic cells around oocyte nests. ESR2 was localized primarily to germ cells, but androgen receptor was exclusively expressed in somatic cells. CYP17A1 and HSD3B2 were also localized to oocytes, whereas CYP11A1 was detected in oocytes and some pregranulosa cells. Conclusions: The human fetal ovary expresses the machinery to produce and detect multiple steroid signaling pathways, including estrogenic signaling, with the oocyte acting as a key component. This study provides a step-change in our understanding of local dynamics of steroid hormone signaling during the key period of human primordial follicle formation.
Teerds et al. (1993) reported that the pattern of immunostaining for 3 beta-HSD remained constant in the interstitial cell compartment. As thecal cells differentiated from the surrounding stroma and restructured around the
secondary follicle, they expressed intense staining for 3 beta-HSD. This staining persisted in preantral, antral, and preovulatory follicles.
Granulosa cells in primary, secondary, and antral follicles did not contain detectable levels of 3 beta-HSD and did not stain positively until the
follicle reached the preovulatory stage of development.