scholarly journals Peptide Regulators in the Ovarian Follicle

1981 ◽  
Vol 34 (6) ◽  
pp. 491 ◽  
Author(s):  
James M Hammond

Data generated within the last several years have shown that follicular fluid contains substances, presumably peptide in nature, which exert potentially important effects on granulosa cells and the oocyte. This review briefly summarizes the current evidence concerning the nature and importance of these putative regulators including the luteinization inhibitor, oocyte maturation inhibitor, inhibitors of the binding of luteinizing hormone and follicle stimulating hormone, stimulators of ornithine decarboxylase and intrafollicular peptides with gonadotrophin-releasing activity. Although the existence of such activities has been clearly demonstrated, the evidence for a regulatory role of these agents in the control of ovarian physiology is not compelling. However, their occurrence must now be taken into account in our attempts to understand the mechanism of follicular growth, differentiation and atresia.

2020 ◽  
Author(s):  
Livio Casarini ◽  
Clara Lazzaretti ◽  
Elia Paradiso ◽  
Silvia Limoncella ◽  
Laura Riccetti ◽  
...  

AbstractClassically, follicle stimulating hormone receptor (FSHR) driven cAMP-mediated signaling boosts human ovarian follicle growth and would be essential for oocyte maturation. However, contradicting in vitro suggest a different view on physiological and clinical significance of FSHR-mediated cAMP signaling. We found that the G protein coupled estrogen receptor (GPER) heteromerizes with FSHR, reprogramming cAMP/death signals into proliferative stimuli fundamental for sustaining oocyte survival. In human granulosa cells, survival signals are effectively delivered upon equal expression levels of both receptors, while they are missing at high FSHR:GPER ratio, which negatively impacts follicle maturation and strongly correlates with FSH responsiveness of patients undergoing controlled ovarian stimulation. Consistent with high FSHR expression levels during follicular selection, cell viability is dramatically reduced in FSHR overexpressing cells due to preferential coupling to the Gαs protein/cAMP pathway. In contrast, FSHR/GPER heteromer formation resulted in FSH-triggered anti-apoptotic/proliferative signaling delivered via the Gβγ dimer while heteromer impairment or GPER-associated Gαs inhibitory protein complexes resulted in cell death. GPER-depleted granulosa cells have an amplified FSH-dependent decrease in cell viability and steroidogenesis, consistent with the requirement of estrogen signaling for successful oocyte growth. Therefore, our findings indicate how oocyte maturation depends on the capability of GPER to shape FSHR selective signals, indicating hormone receptor heteromers may be a marker of cell proliferation.One Sentence SummaryFSHR/GPER heteromers block cAMP-dependent selection of ovarian follicles and target tumor growth and poor FSH-response in women.


2021 ◽  
Vol 22 (23) ◽  
pp. 12735
Author(s):  
Olayiwola O. Oduwole ◽  
Ilpo T. Huhtaniemi ◽  
Micheline Misrahi

Spermatogenesis and folliculogenesis involve cell–cell interactions and gene expression orchestrated by luteinizing hormone (LH) and follicle-stimulating hormone (FSH). FSH regulates the proliferation and maturation of germ cells independently and in combination with LH. In humans, the requirement for high intratesticular testosterone (T) concentration in spermatogenesis remains both a dogma and an enigma, as it greatly exceeds the requirement for androgen receptor (AR) activation. Several data have challenged this dogma. Here we report our findings on a man with mutant LH beta subunit (LHβ) that markedly reduced T production to 1–2% of normal., but despite this minimal LH stimulation, T production by scarce mature Leydig cells was sufficient to initiate and maintain complete spermatogenesis. Also, in the LH receptor (LHR) knockout (LuRKO) mice, low-dose T supplementation was able to maintain spermatogenesis. In addition, in antiandrogen-treated LuRKO mice, devoid of T action, the transgenic expression of a constitutively activating follicle stimulating hormone receptor (FSHR) mutant was able to rescue spermatogenesis and fertility. Based on rodent models, it is believed that gonadotropin-dependent follicular growth begins at the antral stage, but models of FSHR inactivation in women contradict this claim. The complete loss of FSHR function results in the complete early blockage of folliculogenesis at the primary stage, with a high density of follicles of the prepubertal type. These results should prompt the reassessment of the role of gonadotropins in spermatogenesis, folliculogenesis and therapeutic applications in human hypogonadism and infertility.


1983 ◽  
Vol 104 (2) ◽  
pp. 227-232 ◽  
Author(s):  
E. V. YoungLai ◽  
J. F. Jarrell

Abstract. Granulosa cells were harvested from mares at various stages of the oestrous cycle and incubated in Krebs-Ringer bicarbonate buffer with 1β,2β[3H]androstenedione as substrate. The release of 3H2O expressed as cpm/h/mg protein varied from 44 000 to 768 000 in follicles from 7 mares. The release of 3H2O was not significantly altered by luteinizing hormone, follicle stimulating hormone or pregnant mare's serum gonadotrophin. There was a significant negative correlation between the release of 3H2O and the concentration of progesterone in the follicular fluid. Based on the assumption that the release of 3H2O represent total aromatization, these data suggest that the equine granulosa cells have a very active aromatizing enzyme system.


Author(s):  
Kenichiro Sakaguchi ◽  
Yojiro Yanagawa ◽  
Koji Yoshioka ◽  
Tomoko Suda ◽  
Seiji Katagiri ◽  
...  

Abstract Background The antral follicle count (AFC) in mammalian ovaries positively correlates with female fertility. To clarify the causes of differences in fertility between low and high AFC cows, we investigated follicular growth dynamics and hormone concentrations in plasma, follicular fluid, and in vitro growth (IVG) media at different stages of follicular growth. Methods Seven cows were divided into high AFC (n = 4, > 30 follicles) and low AFC (n = 3, < 30 follicles) groups based on the peak AFC detected by ultrasonography. These cows were subjected to estrous synchronization, daily ovarian ultrasonography, and blood collection. Their follicular fluid was collected from dominant follicles at different stages (selection, luteal, and ovulatory phases). In another experiment, we cultured oocyte-cumulus-granulosa cell complexes collected from early antral follicles (< 1 mm) for 12 days. Estradiol-17β (E2), testosterone (T), progesterone (P4), and anti-Müllerian hormone (AMH) concentrations in follicular fluids and plasma were measured. Plasma follicle-stimulating hormone (FSH) concentrations were examined. E2, P4, and AMH concentrations were also measured in IVG media. Results The numbers of small (< 4 mm) and intermediate (4–8 mm) follicles were larger in the high AFC group than in the low AFC group (P < 0.05). The number of intermediate follicles was stable in the low AFC group, indicating consistent development. However, the number of these follicles fluctuated in the high AFC group. Plasma FSH concentrations were higher, whereas E2 and T concentrations were lower in the low AFC group (P < 0.05). E2 concentrations and the E2/P4 ratio in ovulatory follicles and IVG media on day 8 were higher in the high AFC group (P < 0.05). AMH concentrations in plasma and IVG media (P < 0.01) were higher in the high AFC group. Conclusions The weaker response to FSH of granulosa cells caused low E2 production in the low AFC group, resulting in high FSH concentrations and the consistent development of intermediate follicles. Conversely, higher E2 concentrations suppressed FSH secretion in the high AFC group. Granulosa cells in the high AFC group had the ability to produce more AMH than those in the low AFC group throughout IVG culture.


1994 ◽  
Vol 6 (2) ◽  
pp. 127 ◽  
Author(s):  
JK Findlay

The role of the gonadotrophins follicle-stimulating hormone (FSH) and luteinizing hormone and the putative local regulators, activin and follistatin, in the control of folliculogenesis is reviewed. An account of early work on the development and application of assays for FSH and inhibin is given, together with a summary of the data on the ovarian responsiveness to gonadotrophin and follicular atresia. Models for studying local regulation of granulosa cells in vitro are described and the data from these experiments reviewed. It is concluded that activin has a role in the development and maintenance of healthy oestrogenic follicles, preventing premature luteinization, whereas follistatin opposes these effects of activin and promotes luteinization or atresia.


1983 ◽  
Vol 61 (5) ◽  
pp. 472-477 ◽  
Author(s):  
Adriana Lischinsky ◽  
David T. Armstrong

The role of granulosa cells on porcine follicular androgen synthesis was studied. Granulosa cells were cultured for 24 h either in Eagle's minimum essential medium (MEM) or in MEM plus follicle-stimulating hormone (FSH; 1 μg/mL). Thecal preparations were cultured with or without luteinizing hormone (LH), either in MEM, 50% "spent media" from granulosa cells control (MA) or 50% "spent media" from granulosa cells incubated with FSH (MB). In the absence of LH, MB stimulated accumulation of both Δ4-androstenedione (twofold) and testosterone (threefold). MB was found to contain high levels of C21-steroids, including progesterone and material which behaves chromatographically and immunologically like pregnenolone. These amounts of C21-steroids were able to stimulate thecal androgen production. The results suggest that granulosa cells contribute to thecal androgen production by providing steroid substrate. This would provide a means for granulosa cells to control the availability of aromatizable androgens.


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