Granulosa cell stimulation of thecal androgen synthesis

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.

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.


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.


1987 ◽  
Vol 253 (5) ◽  
pp. C625-C632 ◽  
Author(s):  
P. Morley ◽  
D. T. Armstrong ◽  
R. E. Gore-Langton

Because fibronectin is a major secretion product of rat granulosa cells in culture, we have investigated 1) the involvement of endogenous fibronectin in granulosa cell attachment, and 2) the consequences of inhibition of this attachment on follicle-stimulating hormone (FSH)-dependent differentiated responses. Attachment was significantly inhibited for up to 8 h in a concentration-dependent manner by antiserum to rat fibronectin, but not by nonimmune serum. Adsorption of antiserum on fibronectin or addition of exogenous fibronectin eliminated this inhibitory activity. Treatment with antiserum did not significantly alter the FSH-dependent production of adenosine 3',5'-cyclic monophosphate over 2 h or progestins over 48 h, while conversion of testosterone to 17 beta-estradiol over 48 h was suppressed by 60% in the presence of antiserum, regardless of antiserum adsorption on fibronectin. Results indicate that endogenous fibronectin is involved in substratum attachment of rat granulosa cells, but that attachment is not a requisite for FSH responsiveness.


1973 ◽  
Vol 74 (3) ◽  
pp. 449-460 ◽  
Author(s):  
Patrick C. Walsh ◽  
Ronald S. Swerdloff ◽  
William D. Odell

ABSTRACT Serum follicle stimulating hormone (FSH) and luteinizing hormone (LH) were measured by radioimmunoassay in a group of elderly men following castration and oestrogen therapy. Prior to orchiectomy, mean serum concentrations of LH and FSH were within the normal range. Two days following castration, serum LH concentrations increased in all eight patients; higher levels of LH were subsequently measured in all but one patient after periods of time ranging from 49 to 210 days. Serum FSH levels, measured in three patients following castration, increased in a pattern parallel to LH changes. Ethinyl oestradiol (EOe) in doses ranging from 5 to 300 μg/day was administered to ten men who had been castrated 3 to 72 months earlier. Oestrogen treatment suppressed both LH and FSH in a parellel manner in nine of ten patients. LH was first suppressed to intact levels in one of eight patients treated with 20 μg/day of EOe, in two of six patients treated with 50 μg/day, and in one patient by 80 μg/day. FSH was not suppressed to precastration levels until 50 μg/day of EOe was administered; this dose suppressed three of six patients. Higher doses of EOe (150–300 μg/day) suppressed both LH and FSH to levels below the sensitivity of the assay. These data fail to demonstrate any differential effect of oestrogen on LH and FSH release.


2021 ◽  
Vol 22 (4) ◽  
pp. 2047
Author(s):  
Nina Schmid ◽  
Kim-Gwendolyn Dietrich ◽  
Ignasi Forne ◽  
Alexander Burges ◽  
Magdalena Szymanska ◽  
...  

Sirtuins (SIRTs) are NAD+-dependent deacetylases that regulate proliferation and cell death. In the human ovary, granulosa cells express sirtuin 1 (SIRT1), which has also been detected in human tumors derived from granulosa cells, i.e., granulosa cell tumors (GCTs), and in KGN cells. KGN cells are an established cellular model for the majority of GCTs and were used to explore the role of SIRT1. The SIRT1 activator SRT2104 increased cell proliferation. By contrast, the inhibitor EX527 reduced cell numbers, without inducing apoptosis. These results were supported by the outcome of siRNA-mediated silencing studies. A tissue microarray containing 92 GCTs revealed nuclear and/or cytoplasmic SIRT1 staining in the majority of the samples, and also, SIRT2-7 were detected in most samples. The expression of SIRT1–7 was not correlated with the survival of the patients; however, SIRT3 and SIRT7 expression was significantly correlated with the proliferation marker Ki-67, implying roles in tumor cell proliferation. SIRT3 was identified by a proteomic analysis as the most abundant SIRT in KGN. The results of the siRNA-silencing experiments indicate involvement of SIRT3 in proliferation. Thus, several SIRTs are expressed by GCTs, and SIRT1 and SIRT3 are involved in the growth regulation of KGN. If transferable to GCTs, these SIRTs may represent novel drug targets.


Reproduction ◽  
2010 ◽  
Vol 140 (2) ◽  
pp. 295-303 ◽  
Author(s):  
Jennifer L Juengel ◽  
Lisa J Haydon ◽  
Brigitta Mester ◽  
Brian P Thomson ◽  
Michael Beaumont ◽  
...  

IGFs are known to be key regulators of ovarian follicular growth in eutherian mammals, but little is known regarding their role in marsupials. To better understand the potential role of IGFs in the regulation of follicular growth in marsupials, expression of mRNAs encoding IGF1, IGF2, IGF1R, IGF-binding protein 2 (IGFBP2), IGFBP4 and IGFBP5 was localized by in situ hybridization in developing ovarian follicles of the brushtail possum. In addition, the effects of IGF1 and IGF2 on granulosa cell function were tested in vitro. Both granulosa and theca cells synthesize IGF mRNAs, with the theca expressing IGF1 mRNA and granulosa cell expressing IGF2 mRNA. Oocytes and granulosa cells express IGF1R. Granulosa and theca cells expressed IGFBP mRNAs, although the pattern of expression differed between the BPs. IGFBP5 mRNA was differentially expressed as the follicles developed with granulosa cells of antral follicles no longer expressing IGFBP5 mRNA, suggesting an increased IGF bioavailability in the antral follicle. The IGFBP protease, PAPPA mRNA, was also expressed in granulosa cells of growing follicles. Both IGF1 and IGF2 stimulated thymidine incorporation but had no effect on progesterone production. Thus, IGF may be an important regulator of ovarian follicular development in marsupials as has been shown in eutherian mammals.


1978 ◽  
Vol 89 (1) ◽  
pp. 166-172 ◽  
Author(s):  
T. J. Weiss ◽  
D. T. Armstrong ◽  
J. E. A. McIntosh ◽  
R. F. Seamark

ABSTRACT Theca and granulosa tissues isolated from sheep ovarian follicles of different sizes were incubated in the presence of human chorionic gonadotrophin (HCG; 5 IU/ml) or follicle stimulating hormone (FSH; 5 μg NIH-FSH-S11/ml) for 40 min. Changes in the total amounts of cyclic 3′,5′-adenosine monophosphate (cAMP) were used as an index of the responsiveness of these preparations to the hormones. Thecal tissue of both large (4–6 mm in diameter) and small (1–3 mm) follicles responded similarly to gonadotrophins. Granulosa cells from small follicles failed to respond to stimulation by HCG. FSH, however, consistently increased cAMP production in comparison with controls or cells treated with HCG. Granulosa cells of large follicles responded to both HCG and FSH.


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