Stimulation of progesterone secretion by recombinant follistatin-288 in human granulosa cells.

Li, Wei; Khorasheh, Shideh; Yuen, Basil Ho; Ling, Nicholas; Leung, Peter C.K.

doi:10.1210/endo.132.4.8384994

Cited by 21 publications

(8 citation statements)

References 35 publications

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“…We show here for the first time that PGE 2 is able to increase FS production in ovarian granulosa cells, and this finding supports the idea that FS might have luteotropic effects in the human ovary. A luteotropic role for FS in human ovary is also supported by recent studies showing that FS is able to increase human GL cell progesterone production [53], probably by blocking the effects of endogenously produced activins [29]. Although no studies on the stimulatory effect of PGE 2 on FS production have been previously described in ovarian cells, PGE2 has been reported to induce FS mRNA in rat mesangial cells [54].…”

Section: Discussionmentioning

confidence: 80%

Regulation of the Activin-Binding Protein Follistatin in Cultured Human Luteinizing Granulosa Cells: Characterization of the Effects of Follicle Stimulating Hormone, Prostaglandin E2, and Different Growth Factors1

Tuuri

Ritvos

1995

Biology of Reproduction

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Regulation of the activin-binding protein follistatin (FS) by recombinant human (rh) FSH, prostaglandin E2 (PGE2), and several polypeptide growth factors was examined in cultures of human granulosa-luteal (GL) cells obtained from in-vitro fertilization patients at oocyte retrieval. Northern and dot blot hybridization analyses demonstrated that both rhFSH and PGE2 caused stimulatory effects on FS mRNA levels in a culture stage-, time-, and concentration-dependent manner. An 8-h stimulation with rhFSH (100 ng/ml) significantly increased FS mRNA levels on Days 5 and 7 of culture and PGE2 (10(-6)M) on Days 2, 4, and 7. The stimulatory effect of rhFSH and PGE2 on FS mRNA levels were rapid and transient. Maximal inductions occurred 8 h after stimulation, whereas weak or no stimulatory effects were seen at 24 or 48 h. PGF2 alpha did not affect FS mRNA levels at any time point studied. Treatment of the cells with the protein synthesis inhibitor cycloheximide prior to rhFSH stimulation did not inhibit the rapid induction of FS mRNAs, but it prevented the decline at 24 h. Both rhFSH and PGE2 clearly also increased the levels of secreted FS proteins are detected by immunoprecipitation studies with a specific antibody. The effects of the polypeptide growth factors epidermal growth factor (EGF); transforming growth factor beta 1 (TGF beta 1), and activin A on FS mRNA levels were also examined. TGF beta 1 and activin A had no effect on basal FS expression at any concentration or time point studied. An 8-h stimulation with EGF increased FS mRNA levels, but the effect was weaker than those caused by rhFSH and PGE2. We conclude that rhFSH and PGE2 induce FS mRNA and protein in human cultured GL cells. EGF is able to induce FS mRNA to a lesser extent than are rhFSH and PGE2, whereas PGF2 alpha, TGF beta 1, and activin A do not affect basal FS mRNA levels in human cultured GL cells. This study together with our previous report on the stimulatory effect of hCG on FS levels suggest that in the luteal phase of the human menstrual cycle, FS expression in granulosa cells is likely to be positively controlled by luteotropic factors such as gonadotropins and PGE2. Consequently, elevated FS levels may support the survival of the human CL since FS is known to prevent the antisteroidogenic effects of activin in human GL cells.

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Section: Discussionmentioning

confidence: 80%

Regulation of the Activin-Binding Protein Follistatin in Cultured Human Luteinizing Granulosa Cells: Characterization of the Effects of Follicle Stimulating Hormone, Prostaglandin E2, and Different Growth Factors1

Tuuri

Ritvos

1995

Biology of Reproduction

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“…In addition, although follistatin increases progesterone secretion in a dose-dependent manner, it does not augment hCG-stimulated progesterone secretion [30]. We therefore speculate that the follicular volume, and P4, T and ASD levels in the follicular fluid are the cumulative products of high constant FSH stimulation and the ovulatory dose of hCG administered during the process of COH, not necessarily in accordance with the mRNA expression of follistatin at the moment of oocyte retrieval.…”

Section: Discussionmentioning

confidence: 76%

Expression of inhibin-activin subunits, follistatin and smads in granulosa-luteal cells collected at oocyte retrieval

Chang

Kang

Lan

et al. 2006

J Assist Reprod Genet

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Purpose: To examine the expression of inhibinactivin subunits, follistatin, and Smads 2, 3 and 4 in granulosa-luteal cells at the time of oocyte retrieval.Methods: Quantitative reverse transcriptase-polymerase chain reaction was performed to quantify the mRNA expression of the investigated genes: inhibin α-subunit, inhibinactivin βA-and βB-subunits, follistatin, and Smads 2, 3 and 4.Results: α-, βA-and βB-subunits of inhibin-activin, and follistatin were all well expressed in granulosa-luteal cells obtained from either dominant or cohort follicles. α-subunits strongly correlated with Smad2 (p < 0.001). βA-subunit significantly correlated with Smad4, p < 0.001. βB-subunit significantly correlated with Smad2, p = 0.002, and follistatin expression strongly correlated with the expression of Smads 2 and 4 (p < 0.001 and = 0.007 respectively).Conclusions: We found, for the first time that inhibinactivin βB-subunit mRNA was well expressed in human granulosa-luteal cells obtained from either dominant or cohort follicles. α-, βA-and βB-subunits and follistatin cor-

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“…In addition to neutralizing the action of activin, we have also shown that FS alone stimulates basal progesterone, 20ct-hydroxyprogesterone and cAMP accumulation in the human granulosa-luteal cells [49]. FS also stimulates basal estradiol production [Khora- [50] , It is conceivable, therefore, that FS may have actions which are independent of activ in.…”

Section: Biological Actions Of Foiiistatinmentioning

confidence: 97%

Activin and Follistatin as Local Regulators in the Human Ovary

et al. 1996

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There is increasing evidence that activin may act as an autocrine/paracrine regulator of ovarian functions. Activin subunit mRNAs as well as activin immunoreactivities have been detected in the human ovary. Activin alters granulosa cell proliferation and steroidogenesis. The effect of activin is most likely mediated through specific receptors as mRNAs encoding several forms of activin receptors, namely ActR-I, ActR-IB, ActR-II and ActR-IIB are found in the preovulatory follicles as well as in cultured granulosa-luteal cells. Activin-binding protein, follistatin (FS), is also produced in the human ovary. In addition to neutralizing the effect of activin on steroid production, FS on its own also enhances estradiol production, an effect similar to that seen after activin treatment. These findings strongly suggest that activin and FS are important local regulators of steroidogenesis in the human ovary.

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Stimulation of progesterone secretion by recombinant follistatin-288 in human granulosa cells.

Cited by 21 publications

References 35 publications

Regulation of the Activin-Binding Protein Follistatin in Cultured Human Luteinizing Granulosa Cells: Characterization of the Effects of Follicle Stimulating Hormone, Prostaglandin E2, and Different Growth Factors1

Regulation of the Activin-Binding Protein Follistatin in Cultured Human Luteinizing Granulosa Cells: Characterization of the Effects of Follicle Stimulating Hormone, Prostaglandin E2, and Different Growth Factors1

Expression of inhibin-activin subunits, follistatin and smads in granulosa-luteal cells collected at oocyte retrieval

Activin and Follistatin as Local Regulators in the Human Ovary

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