17 beta-Hydroxysteroid dehydrogenases (17 beta-HSDs) are enzymes involved in both the activation and inactivation of androgens and estrogens. 17 beta-HSD type 1 shows a high specificity for C18 steroids and is the major isozyme in the granulosa cells of the ovary. Its role is to convert the inactive C18 steroid estrone to the active estrogen estradiol, which in turn locally promotes maturation of the follicle. Andersson and Moghrabi (1997) reviewed physiology and molecular genetics of 17 beta-hydroxysteroid dehydrogenases. Four distinct 17 beta-HSD isozymes have been characterized so far, and the data strongly suggests that different 17 beta-HSD isozymes have distinct roles in endocrine and intracrine metabolism of sex steroids. Current data suggest that 17 beta-HSD type 1 is the principal isoenzyme involved in glandular estradiol production both in humans and rodents.
NCBI Summary:
Type 1 17 beta-hydroxysteroid dehydrogenase 1 (17-ketosteroid reductase); acts upon C18 steroids
General function
Enzyme, Oxidoreductase
Comment
Cellular localization
Cytoplasmic
Comment
Ovarian function
Steroid metabolism
Comment
Enzymes with 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) activity catalyse reactions between the low-active female sex steroid, estrone, and the more potent estradiol. 17 beta-HSD activity is essential for glandular (endocrine) sex hormone biosynthesis, but it is also present in several extra-gonadal tissues. Hence, 17 beta-HSD enzymes also take part in local (intracrine) estradiol production in the target tissues of estrogen action. Poutanen et al. (1995) reviewed the role of 17 beta-hydroxysteroid dehydrogenase type 1 in endocrine and intracrine estradiol biosynthesis.
Expression regulated by
FSH, LH, Steroids, Growth Factors/ cytokines
Comment
Kaminski et al. (1997) reported that, in cultured rat granulosa cells 17HSD type 1 expression is primarily induced by FSH acting via PKA-dependent pathway and the extent of the induction is modulated by PKC-dependent inhibition and autocrine/paracrine growth factors present in the ovary. Ghersevich et al. (1994) indicate that expression of 17HSD type 1 in rat granulosa cells is under multihormonal regulation. The enzyme is stimulated by FSH, via cAMP, and the effect of FSH is modulated by estrogens, androgens, and EGF.
Ovarian localization
Granulosa
Comment
Akinola et al. (1997) reported that immunohistochemical analysis of rat 17HSD type 1 showed that the enzyme is exclusively expressed in the granulosa cells of developing, healthy, primary, secondary, and tertiary follicles at all stages of the estrous cycle and pregnancy, and is not detected in the corpora lutea. The data showed that the amount of the enzyme expressed in the follicle increases as follicular maturation progresses and is highest in tertiary and Graafian follicles.
Changes in mouse granulosa cell gene expression during early luteinization. McRae RS et al. Changes in gene expression during granulosa cell luteinization have been measured using serial analysis of gene expression (SAGE). Immature normal mice were treated with pregnant mare serum gonadotropin (PMSG) or PMSG followed, 48 h later, by human chorionic gonadotropin (hCG). Granulosa cells were collected from preovulatory follicles after PMSG injection or PMSG/hCG injection and SAGE libraries generated from the isolated mRNA. The combined libraries contained 105,224 tags representing 40,248 unique transcripts. Overall, 715 transcripts showed a significant difference in abundance between the two libraries of which 216 were significantly down-regulated by hCG and 499 were significantly up-regulated. Among transcripts differentially regulated, there were clear and expected changes in genes involved in steroidogenesis as well as clusters of genes involved in modeling of the extracellular matrix, regulation of the cytoskeleton and intra and intercellular signaling. The SAGE libraries described here provide a base for functional investigation of the regulation of granulosa cell luteinization.
Follicle stages
Primary, Secondary, Antral, Preovulatory
Comment
Phenotypes
Mutations
1 mutations
Species: mouse
Mutation name: None
type: None fertility: fertile Comment:
A mouse tool for conditional mutagenesis in ovarian granulosa cells. Grabner B et al. Here we describe the generation of an inducible Cre transgenic line allowing conditional mutagenesis in ovarian granulosa cells. We have expressed the tamoxifen inducible CreER(T2) fusion protein from a Bacterial Artificial Chromosome (BAC) containing the regulatory elements of the hydroxysteroid (17-beta) dehydrogenase 1 (Hsd17b1) gene. Hsd17b1-iCreER(T2) transgenic mice express the iCreER(T2) fusion protein exclusively in ovarian granulosa cells. Recombination analysis at the genomic DNA level using mice with 'floxed' Stat3 alleles showed no Cre activity in absence of tamoxifen whereas tamoxifen treatment induced Cre activity solely in the ovaries. Further characterization of Hsd17b1-iCreER(T2) mice using a Cre reporter line demonstrated that Cre-mediated recombination was restricted to ovarian granulosa cells. Therefore, Hsd17b1-iCreER(T2) mice should be a useful tool to analyze the gene functions in ovarian granulosa cells. (c) 2010 Wiley-Liss, Inc.
A model for inducible KO of granulosa cell genes.