Direct production of gonadal steroids from sulfated adrenal androgens may be an important alternative or complementary pathway for ovarian steroidogenesis.
The conversion of sulfated adrenal androgens. present in serum at micromolar
concentrations in adult women, into unconjugated androgens or estrogens
requires steroid sulfatase (STS) activity.
Steroid sulfatase utilizes DHEAS, an adrenal product, as a substrate for production of
other androgens such as dehydroepiandrosterone (DHEA), androstenedione, and
testosterone.
NCBI Summary:
The protein encoded by this gene catalyzes the conversion of sulfated steroid precursors to estrogens during pregnancy. The encoded protein is found in the endoplasmic reticulum, where it acts as a homodimer. Mutations in this gene are known to cause X-linked ichthyosis (XLI). [provided by RefSeq, Jul 2008]
General function
Comment
Transcriptional control of human steroid sulfatase. Nardi A et al. Steroid sulfatase (STS) is a membrane-bound microsomal enzyme that hydrolyzes various alkyl and aryl steroid sulfates, leading to the in situ formation of biologically active hormones. The entire human STS gene spans over approximately 200kbp of which the first 100kbp include the regulatory region, while the STS-coding region is located downstream. Previous studies indicated that STS expression, in different human tissues, could be regulated by at least six different promoters associated with alternative first exons. Here, we describe two new splicing patterns: the first, found in the prostatic cell line PC3, is based upon a partially coding new first exon (0d) that is spliced to a new second exon (1e). The second variant was found in the ovary and it is characterized by the novel splicing of the untranslated exon 0b to exon 0c, which is then spliced to the common exon 1b. We also report the results of a multiplex ligation-dependent probe amplification (RT-MLPA) analysis for the simultaneous detection, in qualitative and/or semi-quantitative terms, of the transcription patterns of STS in different tissues.
Cellular localization
Cytoplasmic
Comment
In situ estrogen metabolism in proliferative endometria from untreated women with polycystic ovarian syndrome with and without endometrial hyperplasia. Bacallao K et al. (2008) The aim of the present investigation was to study whether the endocrinological status of women bearing polycystic ovarian syndrome (PCOS) affects the endometrial in situ steroid metabolism. For this purpose, we evaluated the mRNA levels (RT-PCR), and the activity of steroid metabolic enzymes: P450 aromatase, steroid sulfatase (STS), estrogen sulfotransferase (EST) and 17beta-hydroxysteroid dehydrogenase (17beta-HSD) in 23 samples of normal endometria (CE), 18 PCOS endometria without treatment (PCOSE), 10 specimens from PCOS women with endometrial hyperplasia (HPCOSE), and 7 endometria from patients with endometrial hyperplasia not associated to PCOS (EH). The data showed lower levels of STS mRNA for PCOSE and HPCOSE (p<0.05, p<0.01, respectively) and of EST for HPCOSE and EH compared to control (p<0.05). However, higher levels for EST mRNA were obtained in PCOSE (p<0.05) versus CE. The mRNA and protein levels for P450 aromatase were undetectable in all analyzed endometria. The relationship between the activities of STS and EST was lower in PCOSE and HPCOSE (p<0.05) versus CE. The ratio between the mRNA from 17beta-HSD type 1/type 2 was higher in PCOSE (p<0.05), whereas, a diminution in the 17beta-HSD type 2 activity was observed in PCOSE (p<0.05). These results indicate that the activity of enzymes related to the steroid metabolism in analyzed PCOSE differ from those found in the CE. Consequently, PCOSE may present an in situ deregulation of the steroid metabolism.//////////////////
Ovarian function
Steroid metabolism
Comment
The potential function of steroid sulphatase activity in steroid production and steroidogenic acute regulatory protein expression. Sugawara T, Fujimoto S. The first step in the biosynthesis of steroid hormones is conversion of cholesterol into pregnenolone. StAR (steroidogenic acute regulatory) protein plays a crucial role in the intra-mitochondrial movement of cholesterol. STS (steroid sulphatase), which is present ubiquitously in mammalian tissues, including the placenta, adrenal gland, testis and ovary, desulphates a number of 3beta-hydroxysteroid sulphates, including cholesterol sulphate. The present study was designed to examine the effect of STS on StAR protein synthesis and steroidogenesis in cells. Steroidogenic activities of COS-1 cells that had been co-transfected with a vector for the cholesterol P450scc (cytochrome P450 side-chain-cleavage enzyme) system, named F2, a StAR expression vector (pStAR), and an STS expression vector (pSTS) were assayed. Whole-cell extracts were subjected to SDS/PAGE and then to Western blot analysis. pSTS co-expressed in COS-1 cells with F2 and pStAR increased pregnenolone synthesis 2-fold compared with that of co-expression with F2 and pStAR. Western blot analysis using COS-1 cells that had been co-transfected with pSTS, F2 and pStAR revealed that StAR protein levels increased, whereas STS and P450scc protein levels did not change. The amount of StAR protein translation products increased when pSTS was added to an in vitro transcription-translation reaction mixture. Pulse-chase experiments demonstrated that the 37 kDa StAR pre-protein disappeared significantly ( P <0.01) more slowly in COS-1 cells that had been transfected with pSTS than in COS-1 cells that had not been transfected with pSTS. The increase in StAR protein level is not a result of an increase in StAR gene expression, but is a result of both an increase in translation and a longer half-life of the 37 kDa pre-StAR protein. In conclusion, STS increases StAR protein expression level and stimulates steroid production.
Clemens JW, et al 2000 reported steroid sulfatase activity (STS) in the rat ovary, cultured granulosa
cells, and a granulosa cell line.
Substantial STS activity was present in
homogenates of rat ovaries, primary cultures of rat granulosa cells, and a
granulosa cell line, as determined by conversion of radiolabeled estrone
sulfate (E1S) to unconjugated estrone. The potent inhibitor estrone sulfamate
eliminated the STS activity. Using E1S as a substrate with microsomes prepared
from a granulosa cell line, the K-m of STS activity was approximately 72 muM,
a value in agreement with previously published data for rat STS. Therefore,
ovarian cells possess STS and can remove the sulfate from adrenal androgens
such as dehydroepiandrosterone sulfate (DHEA-S). Using DHEA-S as a
steroidogenic substrate represents an alternative model for the production of
ovarian steroids versus the "two cell, two gonadotropin" model of ovarian
estrogen synthesis, whereby thecal cells produce androgens from substrate
cholesterol and granulosa cells convert the androgens into estrogens. The
relative contribution of STS activity to ovarian steroidogenesis remains
unclear but may have important physiological and pathophysiological
implications.
Expression regulated by
LH
Comment
Down-regulation of messenger ribonucleic acid encoding an importer of sulfoconjugated steroids during human chorionic gonadotropin-induced follicular luteinization in vivo. Brown KA et al. Members of the organic anion transporting polypeptide (SLCO/OATP) superfamily are capable of importing anionic compounds across the lipid bilayer in a sodium-independent manner. Member 2B1 has been shown to transport few substrates, two of which are dihydroepiandrosterone-3-sulfate (DHEA-S) and estrone-3-sulfate. Steroid sulfatase (STS) catalyses the hydrolysis of these steroids into their unconjugated counterparts. The objective of this study was to investigate the regulation of SLCO2B1 and STS mRNAs during human chorionic gonadotropin (hCG)-induced ovulation/luteinization. The equine SLCO2B1 cDNA was cloned and shown to encode a 709-amino acid protein (OATP2B1) that is highly conserved when compared to mammalian orthologs. RT-PCR/Southern blot analyses were performed to study the regulation of SLCO2B1 and STS transcripts in equine preovulatory follicles isolated between 0 and 39h after hCG treatment. Results showed high levels of SLCO2B1 mRNA expression before hCG, with a marked decrease observed in follicles obtained 24-39h post-hCG (P<0.05). Analyses of isolated granulosa and theca interna cells identified high mRNA expression in both cell types prior to hCG treatment, with granulosa cells showing a more rapid SLCO2B1 mRNA down-regulation. No significant change in STS mRNA was observed in intact follicle walls. However, when both cell types were isolated, a significant decrease in STS mRNA was observed in granulosa cells 24-39h post-hCG. Collectively, these results demonstrate that the hCG-dependent induction of follicular luteinization is accompanied by the down-regulation of SLCO2B1 and STS transcripts. Considering that OATP2B1 can import sulfoconjugated DHEA and estrogens, and that STS can remove the sulfonate moiety from these steroids, their down-regulation in luteinizing preovulatory follicles may provide an additional biochemical basis for the decrease in ovarian 17beta-estradiol biosynthesis after the LH surge.
Haning RV Jr et al 1992 reported steroid sulfatase in the human ovary and placenta.
In 3 pooled ovarian preparations the Km increased
from 14.3 microM in Tris to 33.0 microM in phosphate. There
is no significant difference between the ovarian and placental values for Km in
either Tris or phosphate , and the increase in the Km produced
by phosphate in ovarian tissue was not.
Haning RV Jr et al 1990 reported steroid sulphatase activity in the human ovarian corpus luteum,
stroma, and follicle: comparison to activity in other tissues and
the placenta.
Steroid sulfatase activity was measured in 89 human samples, using
dehydroepiandrosterone sulfate (DHEAS) as substrate. The lowest activity was
that of follicular fluid which was significantly lower than that of other tissues
tested. The steroid sulfatase activity of ovarian tissue taken
collectively (corpus luteum, stroma, and follicles) was higher than that of other
tissues taken collectively (abdominal skin, uterus, and fallopian tube.
These data indicate that the human ovary (particularly the stroma and follicle) is
capable of utilizing DHEAS, an adrenal product, as a substrate for production of
other androgens such as dehydroepiandrosterone (DHEA), androstenedione, and
testosterone.
Follicle stages
Antral, Preovulatory, Corpus luteum
Comment
Localization and gene expression of steroid sulfatase by RT-PCR in cumulus cells and relationship to serum FSH levels observed during in vitro fertilization Otsuka Y, et al .
BACKGROUND: The purpose of this study was to localize the expression of steroid sulfatase (STS) in cumulus cells and to determine the relationship between STS mRNA expression and the serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol and progesterone. METHODS: The subject group included 49 women (29 to 44 years old) for whom in vitro fertilization treatment was indicated. All subjects gave informed consent. One hundred fourteen samples of cumulus-oocyte complex (COC) were obtained under microscopic observation. Part of the COC was stained by STS antibody. RNA was extracted by phenol-chloroform method and real-time PCR was performed. Serum of each patient was collected and was measured by ELISA. RESULTS: Some of the cumulus samples were stained by STS antibody. The expression of STS mRNA in all samples was confirmed by quantitative RT-PCR. Although there was no significant correlation between the level of STS mRNA and the serum levels of estradiol, progesterone and LH, there was a statistically significant negative correlation between the level of STS mRNA expression and the serum level of FSH (n = 105, p = 0.018, r = -0.22). CONCLUSION: These results have demonstrated for the first time the expression of STS in cumulus cells by immunohistological stainings and real-time RT-PCR. STS expression in cumulus cells may be related to the control of the local steroidal environment in the oocyte. Serum FSH may control STS mRNA expression from the results of RT-PCR, although the correlation was low.