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At least 19 recordsLinked to original sources
PubMed2026

Comprehensive analysis of differentially expressed mRNAs, lncRNAs, and miRNAs involved in ovarian differentiation and development in Qihe gibel carp (Carassius gibelio var. Qihe).

Qihe gibel carp (Carassius gibelio var. Qihe) exhibits diverse reproductive modes including gynogenesis and sexual reproduction, yet the molecular mechanisms of ovarian differentiation remain poorly understood. Ovarian tissues at 20, 30, and 60 days after hatching (dah), representing key stages covering early ovarian differentiation and primary oocyte growth, were subjected to whole-transcriptome sequencing. A total of 27,259 mRNAs, 2622 lncRNAs, and 2467 miRNAs were differentially expressed. Cell cycle, transcription, translation, and DNA replication pathways were significantly upregulated from 20 to 60 dah. Oocyte meiosis was enriched from 20 and 30 dah, whereas metabolic pathways (lipid, carbohydrate, and nucleotide metabolism) were enriched from 30 to 60 dah, indicating sequential progression from meiosis initiation to primary oocyte growth with nutrient synthesis. Hub lncRNAs and key ceRNA networks (e.g., MSTRG.28669.5-miR-221-ccnb2) were identified. This study provides the first comprehensive characterization of ncRNA-mediated regulation and ceRNA networks during ovarian development in Qihe gibel carp, establishing a foundation for understanding ovarian differentiation in this species.

Animals↗
PubMed1999

Ovarian differentiation and gonadal failure.

Ovarian failure can result from several different genetic mechanisms-X chromosomal abnormalities, autosomal recessive genes causing various types of XX gonadal dysgenesis, and autosomal dominant genes. The number and precise location of loci on the X are still under investigation, but it is clear that, in aggregate, these genes are responsible for ovarian maintenance, given that monosomy X shows germ cells that undergo accelerated atresia. Despite recent hypotheses, at present there is no evidence for a gene directing primary ovarian differentiation; this process may be constitutive. Phenotypic/karyotypic correlation and limited molecular confirmation have long shown that proximal Xp and proximal Xq contain regions of the most importance to ovarian maintenance. Terminal deletions at Xp11 result in 50% primary amenorrhea and 50% premature ovarian failure or fertility. Deletions at Xq13 usually produce primary amenorrhea. Terminal deletions nearer the telomeres on either Xp of Xq bring about premature ovarian failure more often than complete ovarian failure. The X-linked zinc finger gene (ZFX) and diaphanous 2 Drosophila homologue (DIAPH2) are the only candidate genes for ovarian maintenance that map to the X chromosome. Additional, as yet unidentified, genes along the X chromosome must be involved. The search for these genes in humans is hampered by the lack of candidate genes that map to the X chromosome, the scarcity of patients with fortuitous autosomal translocations, and small pedigrees, which hinder mapping of the loci. In addition, difficulties with human germ cell research also make it challenging to dissect genes important to ovarian development. Autosomal genes also are involved in ovarian differentiation and gonadal failure. Follicle-stimulating hormone receptor and ataxia telangiectasia are examples of autosomal genes known to cause human ovarian failure. Transgenic mouse models point to many other candidate autosomal genes, and sequencing of the human homologues in affected women should lead to the discovery of new genes responsible for human ovarian failure. Identification, functional analysis, and mapping of novel genes specifically expressed in the ovary of mice and women eventually should lead to fruitful dissection of essential genes in mammalian ovarian development and maintenance.

Animals↗
PubMed1997

Cytokeratin cytoskeleton in the differentiating ovarian follicle of the lizard Podarcis sicula Raf.

By immunoblotting and immunocytochemical techniques, we characterized the cytokeratins previously localized by us in the previtellogenic ovarian follicle of Podarcis sicula. Our results show that these cytokeratins correspond to those expressed in the monolayered epithelia. In fact, the immunoblotting analysis showed that the NCL-5D3 antibody, specific for human low molecular weight cytokeratins expressed in monolayered epithelia, reacted with the cytokeratins extracted both from the ovary and from the monolayered intestinal mucosa of Podarcis sicula. Furthermore, this antibody, in this reptile as in humans, clearly immunolabeled sections of corresponding tissues. The organization of the cytokeratin cytoskeleton in the main steps of the ovarian follicle differentiation was also clarified. The reported observations suggest that in Podarcis sicula, the cytokeratin cytoskeleton is absent in the early oocytes. It first appears in the growing oocytes as a thin cortical layer in concomitance with its becoming visible also in the enlarging follicle cells. In the larger follicles, this cytoskeleton appears well organized in intermediate cells and in particular in fully differentiated pyriform cells. In both these cells a cytokeratin network connects the cytoplasm to the oocyte cortex through intercellular bridges. At the end of the previtellogenic oocyte growth, the intense immunolabeling of the apex in the regressing pyriform cells suggests that the cytokeratin, as other cytoplasmic components, may be transferred from these follicle cells to the oocyte. At the end of the oocyte growth, in the larger vitellogenic oocytes surrounded by a monolayer of follicle cells, the cytokeratin constitutes a heavily immunolabeled cortical layer thicker than in the previous stages.

Animals↗
PubMed2005

Neonatal genistein treatment alters ovarian differentiation in the mouse: inhibition of oocyte nest breakdown and increased oocyte survival.

Early in ovarian differentiation, female mouse germ cells develop in clusters called oocyte nests or germline cysts. After birth, mouse germ cell nests break down into individual oocytes that are surrounded by somatic pregranulosa cells to form primordial follicles. Previously, we have shown that mice treated neonatally with genistein, the primary soy phytoestrogen, have multi-oocyte follicles (MOFs), an effect apparently mediated by estrogen receptor 2 (ESR2, more commonly known as ERbeta). To determine if genistein treatment leads to MOFs by inhibiting breakdown of oocyte nests, mice were treated neonatally with genistein (50 mg/kg per day) on Days 1-5, and the differentiation of the ovary was compared with untreated controls. Mice treated with genistein had fewer single oocytes and a higher percentage of oocytes not enclosed in follicles. Oocytes from genistein-treated mice exhibited intercellular bridges at 4 days of age, long after disappearing in controls by 2 days of age. There was also an increase in the number of oocytes that survived during the nest breakdown period and fewer oocytes undergoing apoptosis on Neonatal Day 3 in genistein-treated mice as determined by poly (ADP-ribose) polymerase (PARP1) and deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end-labeling (TUNEL). These data taken together suggest that genistein exposure during development alters ovarian differentiation by inhibiting oocyte nest breakdown and attenuating oocyte cell death.

Animals↗
PubMed1993

Regulation of delta protein kinase C during rat ovarian differentiation.

Studies were undertaken to classify protein kinase C (PKC) forms present in rat corpora lutea and to begin to evaluate their regulation during ovarian differentiation. Hydroxyapatite (HAP) column chromatography of rat luteal tissue revealed the presence of multiple forms of PKC (alpha, beta, delta, zeta). Identification of the PKC isoforms was based upon elution positions from HAP column chromatography and immunoreactivity. The delta PKC isoform was identified as the major Ca(2+)-independent form of PKC present in rat luteal tissue. The Ca(2+)-independent, lipid-dependent phosphorylation of the 80-kDa delta PKC was readily detectable in soluble luteal extracts and was shown to reflect autophosphorylation of delta PKC. To evaluate the regulation of PKC isoforms during ovarian differentiation, PKC protein levels were compared between preovulatory follicle-enriched ovaries and corpora lutea obtained on day 16 of pregnancy. Levels of delta PKC protein were greatly elevated in corpora lutea compared to levels in preovulatory follicles. In contrast, levels of alpha and beta PKC protein remained constant while levels of zeta PKC were slightly higher in the follicular than the luteal extract. Levels of delta PKC mRNA were also higher in corpora lutea than in preovulatory follicles. These results are the first to demonstrate the physiological regulation of delta PKC with follicular differentiation into corpora lutea and implicate a role for this prominent PKC form in the corpus luteum during pregnancy.

Animals↗
PubMed1987

Formation of the hamster zona pellucida in relation to ovarian differentiation and follicular growth.

Using an immunofluorescence technique on ovarian sections, zona-immunoreactive components were detected in the cytoplasm of the oocyte from the beginning of its growth, when it is surrounded by only a thin squamous follicular cell layer, up to the end of its growth. In parallel with oocyte growth, the staining intensity decreased in the ooplasm. No staining was observed in the cytoplasm of the granulosa cells during normal follicular development in adult cyclic females. However, staining of the granulosa cells was observed at some stages of follicular development in immature females. This staining was especially evident in the ovaries of immature females (22 or 26 days old) stimulated with PMSG. In addition, the staining of the granulosa cells was consistently observed in ovaries showing an abnormal histology. Increased staining of the zona at its outer and inner regions could be distinguished in normal follicles, but when staining occurred on the granulosa cells no such pattern was observed over the zona matrix. These studies indicate that the oocyte itself but not the granulosa cells elaborates the native immunogenic material of the zona pellucida. The administration of PMSG at particular stages of ovarian differentiation interferes with follicular development leading to an abnormal extracellular assembly of the zona and its degradation (phagocytosis) by the surrounding granulosa cells.

Animals↗
PubMed1986

Activation of protein kinase C potentiates cyclic AMP production and stimulates steroidogenesis in differentiated ovarian granulosa cells.

Gonadotropin-stimulated steroidogenesis in the differentiating ovarian granulosa cell is mediated through the activation of cAMP-dependent protein kinase, and is also modulated by calcium-dependent mechanisms. Granulosa cells contain calcium-activated, phospholipid-dependent protein kinase (C kinase), and show an increase in phosphatidylinositol turnover in response to GnRH agonist analogs. To evaluate the role of C kinase in ovarian steroidogenesis, the potent phorbol ester, TPA, and the permeant diacylglycerol, OAG, were used to activate C kinase in granulosa cells from PMSG-treated immature rats. Both TPA and OAG caused dose-dependent stimulation of progesterone production without affecting intra- or extracellular cAMP levels. However, the maximum steroid responses to these compounds were less than those stimulated by cAMP. The ED50 for TPA-stimulated progesterone production was 3 nM, which is close to the known Km for activation of C kinase. Stimulation of steroidogenesis was only observed with biologically-active phorbol esters and permeant diacylglycerols such as OAG and DOG. Exposure of granulosa cells to phospholipase C also increased progesterone production in a dose-dependent manner without changing the cAMP content. Although TPA and OAG did not increase basal cAMP production, both agents enhanced the cAMP responses stimulated by hCG and forskolin; likewise, phospholipase C alone did not change cAMP production but caused a dose-dependent increase in the cAMP responses to hCG and forskolin. These results demonstrate that activation of C kinase promotes steroidogenesis in ovarian granulosa cells, and potentiates the activation of adenylate cyclase by hCG and forskolin. Such findings support the possibility that the calcium, phospholipid-dependent enzyme could be involved in the regulation of progesterone production by hormonal ligands such as gonadotropins and GnRH.

Animals↗
PubMed1991

Somatostatin receptors in differentiated ovarian tumors.

The presence of somatostatin receptors was investigated in 57 primary human ovarian tumors using in vitro receptor autoradiography with three different somatostatin radioligands, 125I-[Tyr11]-somatostatin-14, 125I-[Leu8, D-Trp22, Tyr25]-somatostatin-28, or 125I-[Tyr3]-SMS 201-995. Three cases, all belonging to epithelial tumors, were receptor positive; specifically 1 of 42 adenocarcinomas, 1 of 3 borderline malignancies, and 1 of 2 cystadenomas. Four other epithelial tumors (3 fibroadenomas, 1 Brenner tumor), 4 sex cord-stromal tumors (2 fibrothecomas, 2 granulosa cell tumors), and 2 germ cell tumors (1 dysgerminoma, 1 teratoma) were receptor negative. In the positive cases, the somatostatin receptors were localized on epithelial cells exclusively, were of high affinity (KD = 4.6 nmol/l [nanomolar]), and specific for somatostatin analogs. These receptors bound somatostatin-14 and somatostatin-28 radioligands with a higher affinity than the octapeptide [Tyr3]-SMS 201-995. Healthy ovarian tissue had no somatostatin receptors. A subpopulation of relatively well-differentiated ovarian tumors, therefore, was identified pathobiochemically on the basis of its somatostatin receptor content. This small group of somatostatin receptor-positive tumors may be a target for in vivo diagnostic imaging with somatostatin ligands.

Adenocarcinoma↗
PubMed1997

Emergence of an irreversible differentiated subclone from the poorly differentiated ovarian adenocarcinoma cell line AMOC-2 treated with sodium butyrate.

OBJECTIVE: To cast light on the capacity of an ovarian adenocarcinoma to undergo irreversible cellular differentiation, we established clonal cell lines from cultured ovarian carcinoma cells treated with sodium butyrate and examined their phenotypic changes. METHODS: The poorly differentiated ovarian carcinoma cell line AMOC-2 was exposed to 2 mM sodium butyrate for 30 days, and clonal cell lines were established by a dilution plating technique. RESULTS: Five clonal cell lines were established. One of them had a longer doubling time and lower plating efficiency than the parental clone, also demonstrating stronger expression of vimentin and 56 kD cytokeratin. This clone became columnar with pronounced polarity, formed gland-like structures when cultured in collagen gels, and exhibited no tumorigenicity, in contrast to the parental clone. CONCLUSION: Sodium butyrate treatment of AMOC-2 cells can cause phenotypic changes reminiscent of maturation in the Müllerian duct, endocervix, and/or endometrium.

Adenocarcinoma↗
PubMed1994

Steroidogenic enzyme activity and ovarian differentiation in the saltwater crocodile, Crocodylus porosus.

It has been hypothesized that steroid hormone production is involved in sexual differentiation of the gonads in reptiles with temperature-dependent sex determination. We have therefore examined steroidogenic enzymes and ovarian differentiation in Crocodylus porosus embryos incubated at 30 degrees, a temperature producing 100% female hatchlings. delta 5-3 beta-Hydroxysteroid dehydrogenase (3 beta-HSD) activity was detected only in the adrenal gland before, during, and after the period of ovary differentiation. The same pattern was observed during testis differentiation in embryos incubated at 32 degrees (predominantly male-producing). At no stage was 3 beta-HSD activity detected in the gonads. The tritiated water assay was used to measure aromatase enzyme activity in the gonad-adrenal-mesonephric complex (GAM) during development at 30 degrees C. Aromatase activity in the GAM increased during the period of ovary differentiation. In female C. porosus hatchlings, 85% of the aromatase activity within the GAM was derived from the ovary, 10% from the adrenal, and 5% from the regressing mesonephros. The aromatase inhibitors aminoglutethimide and 4-hydroxyandrostenedione significantly reduced aromatase activity in female hatchling GAMs. In some stage 25 embryos incubated at 32.5 degrees, aromatase activity was low in testes and high in ovaries. These observations show that urogenital tissues of C. porosus are steroidogenically active during gonadal differentiation and that increased aromatase enzyme activity accompanies ovary development at 30 degrees. Steroid synthesis in the GAM of C. porosus embryos may involve interaction between the adrenal glands and the gonads.

3-Hydroxysteroid Dehydrogenases↗
PubMed2006

MDCT of the gonadal veins in females with large pelvic masses: value in differentiating ovarian versus uterine origin.

OBJECTIVE: The objective of our study was to determine the usefulness of recognizing the continuity of the gonadal veins to the pelvic mass to differentiate ovarian versus uterine origin on MDCT in females with a large pelvic mass. MATERIALS AND METHODS: Two radiologists interpreted the MDCT images obtained on a monitor, using paging methods, in 86 female patients with a large pelvic mass (> 8 cm) and 40 patients without an abdominopelvic mass as control subjects. The following issues were recorded using a 5-point scale: visualization of gonadal veins and origin determination based on anatomic continuity. Receiver operating characteristic (ROC) curve analysis was performed, and the interobserver differences were checked with kappa statistics. The maximum diameters of the gonadal veins were also measured. With consensus interpretations, the sensitivity, specificity, and accuracy of ovarian origin determination were calculated. RESULTS: Gonadal veins were shown in more than 70% of the subjects in both the control group and the patients with a mass (hereafter referred to as the "mass group"). There was no significant difference in the diameter of the gonadal veins between the control and mass groups and between patients with an ovarian mass and those with a uterine mass. The values for the area under the ROC curve (A(z)) of the two observers for ovarian origin determination were 0.90 and 0.92. The kappa value was 0.48. The sensitivity, specificity, and accuracy were 83.3%, 87.5%, and 84.9%, respectively. CONCLUSION: Gonadal veins can be shown on MDCT with high consistency; MDCT provides useful information for determining the origin of relatively large pelvic tumors arising in females.

Adult↗
PubMed1998

Germ cell kinetics during early ovarian differentiation: an analysis of the oogonial cell cycle and the subsequent changes in oocyte development during the onset of meiosis in the rat.

The aim of this study was the comparison between the mitoses of oogonia and the initial stages of oocyte meiosis. The structural alterations that the germ cell chromatin undergoes during the oogonial mitosis have been compared with those occurring during the G1- and S-phase just before meiosis. Using plastic embedded 1-microm sections of fetal rat ovaries (embryonic days = ED 14-20) labeled with 3H-thymidine and re-embedded for electron microscopy, a study of the structural conditions of the nuclear chromatin has been combined with a kinetic analysis of the oogonial cell cycle and the transitional period into the meiotic prophase. After ovarian differentiation (ED 14) the oogonia show a non-clonal, but strong proliferation. On ED 16, proliferation changes to a clonal pattern and decreases during ED 17. A final increase in 3H-thymidine incorporation on ED 18 characterizes the meiotic S-phase. On ED 19 the nuclear labeling drops to zero. The mitotic cycle of the oogonia lasts 16.5 hr and can be divided into 11 stages according to the concept of El-Alfy and Leblond [(1988) Am. J. Anat., 183:45-56] on the basis of the chromatin pattern. The S-phase (10.0 hours) extends from the telophase-interphase transition through the interphase to early prophase. The postmitotic G1- and S-phases show a more extensive duration, respectively 10 and 11.5 hours, and differ from their oogonial counterparts by the spherical shape of the nuclei from the very beginning. The chromatin pattern is similar until the end of the S-phase and lacks any prophase-like, preleptotenal chromatin condensation before the oocytes exhibit (pre-) leptotenal structures. Once the germ cell has completed a sequence of clonal mitotic divisions, it irrevocably progresses into meiosis. During an extended postmitotic period, the structural characteristics of meiosis emerge stepwise.

Animals↗
PubMed2003

Exposure of neonatal rats to diethylstilbestrol affects the expression of genes involved in ovarian differentiation.

Exposing neonatal rats with the synthetic estrogen, diethylstilbestrol (DES), induces morphological and functional abnormalities in the adult ovary. We examined the events that lead to this condition using female rats that were exposed to DES for the first five days after birth. The expression of steroidogenic acute regulatory protein (StAR) and cholesterol side-chain cleavage cytochrome P450 (P450scc), which are both required for steroidogenesis in the theca/interstitial region was markedly reduced. The expression of Mullerian inhibiting substance (MIS) was transiently increased in small growing follicles in the ovary of DES-treated rats at postnatal day 7 (P7), and the expression profile in the ovary differed between DES- and vehicle oil-treated rats at P14 and P21. The expression of the transcription factor, steroidogenic factor-1 (SF-1), reduced in theca/interstitial cells, but increased in granulosa cells of primary follicles. These results indicate that altered steroidogenesis and MIS production are mechanisms through which DES induces abnormal ovarian development, and support the notion that androgens and MIS are both critical factors in regulating early ovarian differentiation.

Analysis of Variance↗
PubMed1976

Differential ovarian and adrenal vein catheterization.

Twenty-two hirsute women underwent percutaneous adrenal and ovarian vein catheterization to differentiate and localize excessive hormonal output. All studies were done under fluoroscopic control; catheter placement was verified by venography, and blood samples were withdrawn for hormonal analysis. The right ovarian vein was successfully sampled in 42 per cent of attempts; the left ovarian vein, in 75 per cent; the right adrenal vein, in 56 per cent; and the left adrenal vein, in 100 per cent. Bilateral catheterization did not prove clinically useful. First, anatomic variations in venous size and drainage made catheterization and bilateral sampling difficult. Second, adrenal secretion is both episodic and parallel, necessitating both simultaneous catheterization and serial sampling for adequate diagnosis. The stress of the procedure may provoke increased adrenal output. Third, since ovarian secretion is not parallel, and since increased hormone output has been documented in that ovary containing developing follicles or a corpus luteum, distinguishing ovarian dysfunction proved difficult. Finally, for a time-consuming procedure, patient discomfort cannot be disregarded. This technique has not proved to be a reliable means of determining the site of androgen hypersecretion and thus cannot be recommended in the routine evaluation of female hirsutism.

17-Ketosteroids↗
PubMed1993

Effects of sodium butyrate, dimethylsulfoxide and dibutyryl cAMP on the poorly differentiated ovarian adenocarcinoma cell line AMOC-2.

To determine whether the poorly differentiated AMOC-2 human ovarian adenocarcinoma cell line was capable of undergoing differentiation, AMOC-2 cells were exposed to 2 mM sodium butyrate, 2.5% dimethylsulfoxide, or 4 mM dibutyryl cyclic adenosine monophosphate (dibutyryl cAMP) for 6 days. These treatments resulted in growth inhibition, a reduction in clonogenicity and an increase in cellular glycogen content. Significant increases in heat stable alkaline phosphatase activity also occurred after exposure to sodium butyrate. In addition, a thorn-like microfilament structure observed in untreated cells was diminished concomitantly with morphological changes that included flattening, enlargement and extended cytoplasmic processes after exposure to sodium butyrate or dibutyryl cAMP. Furthermore, treatment with sodium butyrate increased the intracellular concentrations of beta-tubulin, vimentin, neurofilaments (M(r) 210,000) and cytokeratin (M(r) 56,000-58,000). These changes were completely reversed after removal of the inducing agent. The findings suggest that treatment of AMOC-2 cells with sodium butyrate induced a more differentiated phenotype, although terminal differentiation was not achieved.

Adenocarcinoma↗
PubMed2006

Sustained response to bevacizumab in refractory well-differentiated ovarian neoplasms.

BACKGROUND: Bevacizumab has demonstrated activity against a variety of solid tumors, including ovarian carcinoma. However, there have not been reproducible prognostic features associated with its activity. CASES: One patient each with recurrent, refractory well-differentiated serous-endometrioid ovarian carcinoma, micropapillary serous carcinoma of the ovary, and primary peritoneal micropapillary serous carcinoma were treated with single agent bevacizumab (15 mg/kg [DOSAGE ERROR CORRECTED] intravenously every 3 weeks). All three have had dramatic sustained responses of 15, 15, and 22 months' duration. CONCLUSION: Bevacizumab may have significant activity against well-differentiated ovarian carcinoma and micropapillary serous carcinomas of the ovary or peritoneum. Since these tumors are generally indolent and not responsive to adjuvant therapy, further investigation is warranted.

Adult↗
PubMed1995

Diagnostic and biological determinants in undifferentiated and poorly differentiated ovarian carcinomas.

Six ovarian undifferentiated carcinomas (UCs) and 19 poorly differentiated serous (14 cases) and endometrioid (5 cases) carcinomas with areas of solid diffuse carcinomas have been considered for the study. Pathological findings were analyzed in conjunction with molecular analysis concerning the structure and expression of nm23-H1 gene. Differences in the frequency of loss of heterozigosity (LOH) of this gene have been observed between the two groups, UCs displaying lower percentage of LOH (1/5) as compared to poorly differentiated tumors (17/17). The remaining 3 cases (1 UC and 2 poorly differentiated carcinomas) were homozygotes, i.e., noninformative. UCs might occur as a consequence of cellular dedifferentiation, being at the end of the differentiation spectrum of epithelial ovarian tumors. Nevertheless, this study suggests that, in a fraction of cases, UCs could represent a distinct entity not involved in the malignant progression, associated with peculiar DNA anomalies, one possibly being that of the nm23-H1 deletion. In other words, a noticeable subset of UCs, not harboring nm23-H1 alterations, may be histologically uncommitted "ab initio". Moreover, nm23-H1 LOHs could be considered early events in the ovarian carcinogenesis, because similar molecular patterns were found both in primary and metastatic sites of the same tumor.

Biomarkers, Tumor↗
PubMed2000

Apparently normal ovarian differentiation in a prepubertal girl with transcriptionally inactive steroidogenic factor 1 (NR5A1/SF-1) and adrenocortical insufficiency.

Steroidogenic factor 1 (NR5A1/SF-1) plays an essential role in the development of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes, controlling expression of their many important genes. The recent description of a 46,XY patient bearing a mutation in the NR5A1 gene, causing male pseudohermaphroditism and adrenal failure, demonstrated the crucial role of SF-1 in male gonadal differentiation. The role of SF-1 in human ovarian development was, until now, unknown. We describe a phenotypically and genotypically normal girl, with signs and symptoms of adrenal insufficiency and no apparent defect in ovarian maturation, bearing a heterozygote G-->T transversion in exon 4 of the NR5A1 gene that leads to the missense R255L in the SF-1 protein. The exchange does not interfere with protein translation and stability. Consistent with the clinical picture, R255L is transcriptionally inactive and has no dominant-negative activity. The inability of the mutant (MUT) NR5A1/SF-1 to bind canonical DNA sequences might offer a possible explanation for the failure of the mutant protein to transactivate target genes. This is the first report of a mutation in the NR5A1 gene in a genotypically female patient, and it suggests that NR5A1/SF-1 is not necessary for female gonadal development, confirming the crucial role of NR5A1/SF-1 in adrenal gland formation in both sexes.

Adrenal Gland Diseases↗