Hormone Receptor In Granulosa Cells Research Articles

WITHDRAWN: Growth hormone improves insulin-like growth factor 1 and steroid hormone levels in follicle fluid, expression of hormone receptors in granulosa cells, and in vitro fertilization outcomes of poor ovarian responders

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Follicular hormone dynamics during the midcycle surge of gonadotropins in women undergoing fertility treatment.

Changes in concentrations of intra-follicular hormones during ovulation are important for final oocyte maturation and endometrial priming to ensure reproductive success. As no human studies have investigated these changes in detail, our objective was to describe the dynamics of major follicular fluid (FF) hormones and transcription of steroidogenic enzymes and steroid receptors in human granulosa cells (GCs) during ovulation. We conducted a prospective cohort study at a public fertility clinic in 2016-2018. Fifty women undergoing ovarian stimulation for fertility treatment were included. From each woman, FF and GCs were collected by transvaginal ultrasound-guided follicle puncture of one follicle at two specific time points during ovulation, and the study covered a total of five time points: before ovulation induction (OI), 12, 17, 32 and 36h after OI. Follicular fluid concentrations of oestradiol, progesterone, androstenedione, testosterone, 17-hydroxyprogesterone, anti-Mullerian hormone, inhibin A and inhibin B were measured using ELISA assays, and a statistical mixed model was used to analyse differences in hormone levels between time points. Gene expression of 33 steroidogenic enzymes and six hormone receptors in GCs across ovulation were assessed by microarray analysis, and selected genes were validated by quantitative reverse transcription PCR. We found that concentrations of oestradiol, testosterone, progesterone, AMH, inhibin A and inhibin B (P< 0.001) and gene expression of 12 steroidogenic enzymes and five receptors (false discovery rate < 0.0001) changed significantly during ovulation. Furthermore, we found parallel changes in plasma hormones. The substantial changes in follicular hormone production during ovulation highlight their importance for reproductive success.

Gene expression of follicle-stimulating hormone receptors in granulosa cells in poor ovarian responders

Women with poor ovarian response do not produce adequate follicles and express low estradiol levels after standard ovarian stimulation protocols; therefore, their chances of becoming pregnant are reduced. The follicle-stimulating hormone (FSH) binds to specific follicle-stimulating hormone receptors (FSHRs) in the ovary, thereby activating adenylyl cyclase/cyclic adenosine monophosphate, a gene expression regulator. The present study aimed to evaluate whether the FSHR levels in poor ovarian responders differed from those in normal ovarian responders. This cross-sectional study was conducted in the Cipto Mangunkusomo’s Hospital. The study cohort included women with poor ovarian responses (n = 17) and control women with normal ovarian responses (n = 17) who underwent IVF procedures. The FSHR levels in ovarian tissues were measured using qPCR and then compared between the two groups. No statistically significant differences were found in the FSHR levels between the groups. A polymorphism mutation may be present in the FSHR gene of poor ovarian responders.

Poor ovarian response to gonadotropin stimulation is associated with low expression of follicle-stimulating hormone receptor in granulosa cells

Poor ovarian response to gonadotropin stimulation is associated with low expression of follicle-stimulating hormone receptor in granulosa cells

Poor ovarian response to gonadotropin stimulation is associated with low expression of follicle-stimulating hormone receptor in granulosa cells

To explore the importance of follicle-stimulating hormone receptor (FSHR) in granulosa cells in the ovarian response to gonadotropin stimulation. Prospective study. A women's hospital in China. One hundred infertile women undergoing ovarian stimulation with recombinant follicle-stimulating hormone (rFSH). These women were divided into three groups: poor, moderate, and high responders, according to the number of follicles with diameter >/=14 mm. The FSHR expression at both mRNA and protein levels was determined by either reverse transcription-polymerase chain reaction or Western blot in granulosa cells. E(2) concentrations in serum and FSH levels in serum/follicular fluid (FF) were measured by electrochemiluminescence immunoassay. Relative expression of mRNA and protein of FSHR in granulosa cells, serum E(2), FSH level in serum and FF, and the number of mature follicles. The expression of FSHR, at both the mRNA and protein levels, was significantly different among the three groups, with the lowest expression in the poor responders. The level of FSHR protein was positively correlated with the peak level of serum E(2) and the number of mature oocytes. FSH levels in FF and the dosage of rFSH used were significantly different among the three groups, with the highest values in the poor responders. Different levels of FSHR expression in granulosa cells result in different ovarian response, and lower expression of FSHR may account for poor ovarian response to gonadotropin stimulation, which suggests the critical role of FSHR in the ovarian response to gonadotropin stimulation.

Aggregation of luteinizing hormone receptors in granulosa cells: a possible mechanism of desensitization to the hormone.

The temporal relationship between redistribution of receptors to lutropin (luteinizing hormone)/human chorionic gonadotropin in cultured rat ovarian granulosa cells and the cellular response to hormonal challenge were studied. Visualization of receptor-bound human chorionic gonadotropin by indirect immunofluorescence, with hormone-specific antibodies after fixation with 2% formaldehyde, revealed the existence of small clusters around the entire cell circumference 5--20 min after exposure to the hormone at 37 degrees C. Such small receptor aggregates were also evident if hormone incubation was at 4 degrees C or if cells were fixed with 2% formaldehyde before incubation. Larger clusters were evident after prolonged incubation with the hormone (2--4 hr) at 37 degrees C. The later change coincided with diminished cyclic AMP accumulation in respose to challenge with fresh hormone. When the fixation step was omitted and antibodies to human chorionic gonadotropin were applied after hormonal binding, acceleration of both receptor clustering and the desensitization process was observed. This maneuver also induced capping of the hormone receptors. In contrast, monovalent Fab' fragments of the antibodies were without effect. Internalization of the bound hormone in lysosomes, and subsequent degradation, was evident 8 hr after hormonal application and was not accelerated by the antibodies. It is suggested that clustering of the luteinizing hormone receptors may play a role in cellular responsiveness to the hormone. Massive aggregation of the receptors may desensitize the cell by interferring with coupling to adenylate cyclase.

A Previously Undescribed Role for Luteinizing Hormone (LH:hCG) on Follicular Cell Differentiation*

Experiments were designed to determine if an ovulatory dose of human CG (hCG) could act on ovarian preantral follicles to modify the ability of FSH to stimulate follicular growth and to increase the number of gonadotropic hormone receptors in granulosa cells. Hypophysectomized, immature rats were primed with 2.0 mg estradiol or vehicle for 3 days. Subsequently, groups of rats received either 2 μg human FSH (hFSH), 5 IU hCG, hFSH followed 12 h later by hCG, or hCG followed 12 h later by hFSH. In estradiol-primed rats hFSH stimulated a transitory increase in granulosa cell LH receptor by 24 h and an 1.5-fold increase in FSH receptor by 12 h. hCG alone had little or no effect. In contrast, hCG followed by hFSH stimulated a dramatic 15-fold increase in LH receptor by 36 h, a 3-fold increase in FSH receptor by 48 h, and marked development of antral follicles. hFSH followed by hCG also resulted in pronounced follicular growth and marked increases in LH and FSH receptors in granulosa cells. Neither estradiol (2....