Direct Inhibitory Effect of Gonadotropin-Releasing Hormone upon Follicle-Stimulating Hormone Induction of Luteinizing Hormone Receptor and Aromatase Activity in Rat Granulosa Cells*

Hsueh, Aaron J. W.; Wang, C.; Erickson, Gregory F.

doi:10.1210/endo-106-6-1697

Cited by 158 publications

(40 citation statements)

References 32 publications

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“…In (24). The cells were cultured in McCoy's 5a medium supplemented with 2 mM L-glutamine, 100 ,ug of penicillin per ml, 100 ,ug of streptomycin sulfate per ml, and 100 nM A4-androstenedione.…”

mentioning

confidence: 99%

Transcriptional regulation of the rat tissue type plasminogen activator gene: localization of DNA elements and nuclear factors mediating constitutive and cyclic AMP-induced expression.

Ohlsson¹,

Leonardsson²,

Jia³

et al. 1993

Mol. Cell. Biol.

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We have characterized tissue type plasminogen activator (tPA) promoter elements and nuclear factors required for follicle-stimulating hormone (FSH)-induced transcription of the rat tPA gene in granulosa cells and constitutive expression of the gene in the rat neuroblastoma cell line B103. Run-on transcription analysis of isolated nuclei revealed that B103 cells transcribe the tPA gene at a high and constitutive level, while FSH was found to induce tPA gene transcription in a rapid and transient manner in granulosa cells. The maximal FSH-induced transcription rate was obtained after 20 min and was similar in the absence or presence of the protein synthesis inhibitor cycloheximide. However, in the presence of cycloheximide, tPA transcription was not turned off but continued at a high rate for several hours. This phenomenon may at least partly explain the earlier finding that tPA mRNA is superinduced by FSH in the presence of cycloheximide. DNase I footprinting analysis of the first 621 bp of the tPA promoter revealed a total of six regions that interact with nuclear factors from B103 and granulosa cells. Deletion of the promoter region from positions -269 to -621, a region that includes the two most-upstream footprints, had no effect on constitutive or FSH-induced transcription in transient expression experiments. Nuclear extracts from both granulosa cells and B103 cells showed strong binding to a consensus cyclic AMP-responsive element (CRE) at positions -178 to -185 and a neighboring binding site for nuclear factor 1 (NF1) at positions -145 to -158. The factors binding to these two regions were identified as members of the CRE-binding protein and NF1 families of transcription factors, respectively. Footprints were also obtained over two GC boxes at positions -64 to -71 and -41 to -49. These footprints were more pronounced with nuclear extracts from B103 cells than with extracts from untreated or FSH-treated granulosa cells, but gel shift assays indicate that similar amounts of two distinct factors bind to the two GC boxes in both cell types. Transfection experiments using promoter constructs with inactivated promoter elements indicate that both the CRE and NF1 sites contribute to the FSH responsiveness of the rat tPA gene in granulosa cells, while only the NF1 site is important for constitutive expression in B103 cells. The two GC boxes were found to be necessary both for constitutive expression in B103 cells and for FSH-induced expression in granulosa cells, and inactivation of both GC boxes essentially eliminated the tPA promoter activity in both cell types.

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confidence: 99%

Transcriptional regulation of the rat tissue type plasminogen activator gene: localization of DNA elements and nuclear factors mediating constitutive and cyclic AMP-induced expression.

Ohlsson¹,

Leonardsson²,

Jia³

et al. 1993

Mol. Cell. Biol.

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“…In contrast to the complete disappearance of the signal in the CL-like structures, the expression of LH receptor mRNA was still strong in the granulosa cells of the remaining mature follicles. These results suggest that the suppression of the FSH-induced LH receptor expression by a GnRH agonist (Hsueh et al, 1980) would be accompanied by cellular differentiation of granulosa to luteal cells. The present finding that a GnRH antagonist could potentiate FSH-induced LH receptor mRNA expression in the granulosa cells as well as follicular development supports the idea of the existence of an endogenous GnRH molecule in the rat ovary suggested previously by Birnbaumer et al (1985).…”

Section: Discussionmentioning

confidence: 80%

“…A number of studies have demonstrated that GnRH inhibits LH receptor expression in FSH-stimulated growing follicles (Hsueh et al, 1980), mature follicles (Piquette et al, 1991), and corpora lutea (Harwood et al, 1980), suggesting that GnRH is a common suppresser of LH receptor expression in many ovarian cell populations. In the present study, we performed a histological examination of the effects of GnRH Fig.…”

Section: Discussionmentioning

confidence: 99%

“…For example, as stimulatory effects, GnRH was demonstrated to act on mature follicles to induce ovulation (Hsueh et al, 1988) and meiotic maturation of oocytes (Hillensjö and LeMaire, 1980;Banka and Erickson, 1985). On the other hand, as inhibitory effects, GnRH was shown to inhibit the action of follicle stimulating hormone (FSH), such as the induction of luteinizing hormone (LH) receptor and aromatase activity in the premature follicles (Hsueh et al, 1980). The direct induction of apoptosis by GnRH was also demonstrated in the granulosa cells of growing follicles (Billig et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

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Direct Ovarian Effects of a GnRH Agonist in Hypophysectomized Immature Rats: Inhibition of Theca-Interstitial Luteinizing Hormone Receptor mRNA Expression and Induction of Interstitial Cell Differentiation

et al. 2000

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“…Intact iminature female Sprague-Dawley rats (21 -22 days old) were implanted with a 10-rnm silastic capsule containing approximately 10 nig diethylstilbestrol, and fed rat chow and water ad libitum. A 12-h light/ 12-h dark cycle was maintained with the light cycle initiated at 6 a.m. After 4 days the animals were killed using CO,, ovaries removed and granulosa cells released by needle puncture as previously described (Hsueh et al, 1980). The cells were cultured in McCoy's 5a medium supplemented with 2 mM L-glutamine, 100 yglml penicillin, 100 pg/ml streptomycin sulfate, and 100 nM d4-androstenedione.…”

Section: Reagents and Hormonesmentioning

confidence: 99%

Characterisation of the Rat Tissue‐Type Plasminogen Activator Gene Promoter

Leonardsson¹,

Ny²

1997

European Journal of Biochemistry

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Tissue-type plasminogen activator (tPA) activates plasminogen to the active protease plasmin and is implicated in many biological processes that require extracellular proteolysis. In rat ovarian cells, gonadotropins induce the tPA gene by a CAMP-dependent pathway and this induction correlates with the time of follicular rupture. We have previously identified several promoter elements within the first 621 bp of the rat tPA promoter that are important for constitutive and CAMP-induced expression of the gene, including a cAMP responsive element (CRE), a nuclear factor 1 (NF1) element, a SPI-binding site and a G+C-rich box. In this report we have extended our study by analysing promoter constructs, ranging in size from 7.7 kb to 135 bp fused to the luciferase reporter gene. Transient transfection analysis of rat granulosa cells and human 293 cells, reveal that the proximal 268 bp of the promoter is enough to confer high basal and CAMP-induced expression of the gene. At position -162 to -172, between the previously identified CRE and NF1 sites, a novel TAAT-containing promoter element was identified. Mutational inactivation of the TAAT motif indicates that this element is important for both constitutive and CAMP-induced expression of the gene, and for the binding of a presumably novel nuclear factor that we have termed tPA promoter factor-I (tPF-1).

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Direct Inhibitory Effect of Gonadotropin-Releasing Hormone upon Follicle-Stimulating Hormone Induction of Luteinizing Hormone Receptor and Aromatase Activity in Rat Granulosa Cells*

Cited by 158 publications

References 32 publications

Transcriptional regulation of the rat tissue type plasminogen activator gene: localization of DNA elements and nuclear factors mediating constitutive and cyclic AMP-induced expression.

Transcriptional regulation of the rat tissue type plasminogen activator gene: localization of DNA elements and nuclear factors mediating constitutive and cyclic AMP-induced expression.

Direct Ovarian Effects of a GnRH Agonist in Hypophysectomized Immature Rats: Inhibition of Theca-Interstitial Luteinizing Hormone Receptor mRNA Expression and Induction of Interstitial Cell Differentiation

Characterisation of the Rat Tissue‐Type Plasminogen Activator Gene Promoter

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