NCBI Summary:
Sulfotransferase enzymes catalyze the sulfate conjugation of many hormones, neurotransmitters, drugs, and xenobiotic compounds. These cytosolic enzymes are different in their tissue distributions and substrate specificities. The gene structure (number and length of exons) is similar among family members. This gene encodes a protein that transfers a sulfo moiety to and from estrone, which may control levels of estrogen receptors.
Human Chorionic Gonadotropin-Dependent Upregulation of Genes Responsible for Estrogen Sulfoconjugation and Export in Granulosa Cells of Luteinizing Preovulatory Follicles. Brown KA et al. Estrogen sulfotransferase (EST) is responsible for the sulfoconjugation of estrogens, thereby changing their physical properties and preventing their action via the estrogen receptors. These sulfoconjugated steroids no longer diffuse freely across the lipid bilayer, instead, they are exported by members of the ATP-binding cassette family, like ABCC1. The objective of this study was to investigate the regulation of EST and ABCC1 during human chorionic gonadotropin (hCG)-induced ovulation/luteinization. The transcripts for EST and ABCC1 were cloned by RT-PCR and the regulation of their mRNAs was studied in preovulatory follicles obtained during estrus at 0, 12, 24, 30, 33, 36 and 39 h after hCG. Results obtained from RT-PCR/Southern blot analyses showed significant changes in steady-state levels of both EST and ABCC1 mRNA after hCG treatment (P < 0.05). In granulosa cells, a significant increase in EST transcript was observed 30-39 h post-hCG. Similarly, ABCC1 transcript levels were induced in granulosa cells 12-39 h post-hCG. In contrast, no significant changes in either EST or ABCC1 were detected in theca interna samples after hCG. The increase in EST and ABCC1 transcripts observed in granulosa cells was reflected in preparations of intact follicle walls, suggesting that the granulosa cell layer contributes the majority of EST and ABCC1 expression in preovulatory follicles. The present study demonstrates that follicular luteinization is not only accompanied by a decrease in 17beta-estradiol biosynthesis, but also with an increase in expression of genes responsible for estrogen inactivation and elimination from granulosa cells, such as EST and ABCC1, respectively.
Follicle stages
Preovulatory
Comment
Genomewide discovery and classification of candidate ovarian fertility genes in the mouse. Gallardo TD et al. Female infertility syndromes are among the most prevalent chronic health disorders in women, but their genetic basis remains unknown because of uncertainty regarding the number and identity of ovarian factors controlling the assembly, preservation, and maturation of ovarian follicles. To systematically discover ovarian fertility genes en masse, we employed a mouse model (Foxo3) in which follicles are assembled normally but then undergo synchronous activation. We developed a microarray-based approach for the systematic discovery of tissue-specific genes and, by applying it to Foxo3 ovaries and other samples, defined a surprisingly large set of ovarian factors (n = 348, approximately 1% of the mouse genome). This set included the vast majority of known ovarian factors, 44% of which when mutated produce female sterility phenotypes, but most were novel. Comparative profiling of other tissues, including microdissected oocytes and somatic cells, revealed distinct gene classes and provided new insights into oogenesis and ovarian function, demonstrating the utility of our approach for tissue-specific gene discovery. This study will thus facilitate comprehensive analyses of follicle development, ovarian function, and female infertility. This is expressed highly in cumulus cells and oocyte.
Phenotypes
Mutations
1 mutations
Species: mouse
Mutation name: None
type: null mutation fertility: subfertile Comment: Low expression of COX-2, reduced cumulus expansion, and impaired ovulation in SULT1E1-deficient mice. Gershon E et al. The SULT1E1-encoded estrogen sulfotransferase (EST) catalyzes sulfation of estrogen, resulting in its inactivation. Reduced fertility observed in SULT1E1 knockout (KO) female mice has previously been attributed to the deleterious effect of chronic exposure to high levels of circulating estrogen on placental function. We herein suggest that, in addition to placental dysfunction, this phenotype demonstrates that an excess of estrogen impairs ovulation. The role of SULT1E1 in ovulation is suggested by the substantially low ovulatory response in hCG-treated SULT1E1 KO mice; a similar effect was observed when 17beta-estradiol was administered to wild-type (WT) females. The normal rate of ovulation in SULT1E1 KO females may be restored by PGE2. Along this line, ovaries of human Chorionic Gonadotropin (hCG)-treated SULT1E1 KO mice expressed low levels of cyclooxygenase-2 (COX-2) and its downstream TSG6; moreover, their ovaries contained a reduced number of expanded cumuli. Our results demonstrate, for the first time, that estrogen inactivation may allow the expression of COX-2 and subsequent cumulus expansion, enabling normal ovulation. Our findings may be applied to novel treatments of human ovulatory failure.