Hormonal Regulation of Luteinizing Hormone/Chorionic Gonadotropin Receptor mRNA in Rat Ovarian Cells during Follicular Development and Luteinization

Segaloff, Deborah L.; Wang, Haiyun; Richards, JoAnne S.

doi:10.1210/mend-4-12-1856

Cited by 223 publications

(115 citation statements)

References 53 publications

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“…Similarly, follicle-stimulating hormone and PMSGdependent induction of LH receptor mRNA in granulosa cells of preovulatory follicles and its expression in corpora lutea (34,35) occurred normally in PRKO ovaries (not shown). Thus, granulosa cells of preovulatory follicles in PRKO mice have a normal ability to respond to gonadotropins.…”

Section: Ovarian Expression Of Prmentioning

confidence: 79%

“…In situ hybridization was performed according to the detailed methods of Wilkensen (30) and as described (31). 35 S-UTP-labeled antisense and sense probes for cathepsin L and ADAMTS-1 were synthesized from the cloned PCR cDNAs (above) by using the Riboprobe In Vitro Transcription Systems kit (Promega). Slides were dipped in photographic NTB-2 emulsion (Kodak) and exposed at 4°C for 1-3 days.…”

Section: Reverse Transcription-pcr (Rt-pcr)mentioning

confidence: 99%

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Progesterone-regulated genes in the ovulation process: ADAMTS-1 and cathepsin L proteases

Robker

Russell

Espey

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

478

358

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Ovulation is a precisely timed process by which a mature oocyte is released from an ovarian follicle. This process is initiated by the pituitary surge of luteinizing hormone (LH), is temporally associated with transcriptional regulation of numerous genes, and is presumed to involve the synthesis and͞or activation of specific proteases that degrade the follicle wall. The progesterone receptor (PR), a nuclear receptor transcription factor, is induced in granulosa cells of preovulatory follicles in response to the LH surge and has been shown to be essential for ovulation, because mice lacking PR fail to ovulate and are infertile. Using these mice as a model in which to elucidate PR-regulated genes in the ovulation process, we show that the matrix metalloproteinases MMP-2 and MMP-9 are not targets of PR during ovulation. In contrast, two other proteases, ADAMTS-1 (A disintegrin and metalloproteinase with thrombospondin-like motifs) and cathepsin L (a lysosomal cysteine protease), are transcriptional targets of PR action. ADAMTS-1 is induced after LH stimulation in granulosa cells of preovulatory follicles and depends on PR. Cathepsin L is induced in granulosa cells of growing follicles by follicle-stimulating hormone, but the highest levels of cathepsin L mRNA occur in preovulatory follicles in response to LH in a PR-dependent manner. The identification of two regulated proteases in the ovary, together with their abnormal expression in anovulatory PR knockout mice, suggests that each plays a critical role in follicular rupture and represents a major advance in our understanding of the proteolytic events that control ovulation.

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Section: Ovarian Expression Of Prmentioning

confidence: 79%

Section: Reverse Transcription-pcr (Rt-pcr)mentioning

confidence: 99%

Progesterone-regulated genes in the ovulation process: ADAMTS-1 and cathepsin L proteases

Robker

Russell

Espey

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

478

358

View full text Add to dashboard Cite

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“…Our original hypothesis was that LHr expression in granulosa cells was hormonally controlled either directly by E 2 or indirectly through LH stimulation of thecal androgen production and would only be expressed in animals with adequate LH support. Previous studies had shown that induction of granulosal LHr in rodents was dependent upon both FSH and E 2 concentrations (Segaloff et al 1990). Accordingly, in cattle, increases in E 2 concentrations preceded LHr mRNA expression in granulosa cells (Bodensteiner et al 1996, Evans & Fortune 1997).…”

Section: Discussionmentioning

confidence: 96%

Gonadotropin requirements for dominant follicle selection in GnRH agonist-treated cows

Hampton¹,

Bader²,

Lamberson³

et al. 2004

Reproduction

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A study was conducted to examine the effects of gonadotropins on ovarian follicular development and differentiation in GnRH agonist (GnRHa)-treated cattle. Holstein cows were allotted into two pre-treatment groups: controls (n 5 5) and GnRHa-treated (n 5 9). Ovaries were removed from control cows on day 5 following a synchronized estrus. Treatment with GnRHa resulted in follicular arrest at < 5 mm. Following follicular arrest, GnRHa-treated cows received a constant infusion of FSH for 96 h (GnRHa/FSH), with a randomly selected subset receiving hourly pulses of LH in addition to FSH during the last 48 h of infusion (GnRHa/FSH 1 LH). At the end of infusion, ovaries were removed, follicles were counted and measured, and follicular fluid samples were collected from large follicles (>10 mm). Differences in expression of mRNA for LH receptor, FSH receptor, cytochrome P450 side-chain cleavage, 3b-hydroxysteroid dehydrogenase, cytochrome P450 17a-hydroxylase (P450c17) and cytochrome P450 aromatase were determined in large follicles using in situ hybridization. The number of large follicles did not differ between GnRHa/FSH-treated and GnRHa/FSH 1 LH-treated cows (P 5 0.64), but was greater than control animals (P # 0.004). Follicular fluid concentrations of estradiol-17b and androstenedione were highest in GnRHa/FSH 1 LH-treated cows (P # 0.04), intermediate in control cows, and lowest in GnRHa/FSH-treated cows. Hybridization intensity of P450c17 was greater in GnRHa/FSH 1 LH-treated versus control or GnRHa/FSH-treated cows (P # 0.03). These results indicate that while FSH can support bovine follicular growth >10 mm, LH increases androgen production and expression of P450c17.

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“…DISCUSSION LH receptor expression during follicular development, ovulation, and luteinization is highly regulated (5,6). The differences in LH receptor expression are associated with concomitant changes in the steady state levels of LH receptor mRNA (5,6,8,9,36,37). Our previous studies have shown that LRBP might be a trans-acting factor in regulating LH receptor mRNA levels in the ovary (8,9,25,26).…”

Section: Fig 6 Mevalonate Kinase-depleted Lrbp Preparation Shows Dementioning

confidence: 89%

Isolation and Characterization of a Novel trans-Factor for Luteinizing Hormone Receptor mRNA from Ovary

Nair

Menon

2004

Journal of Biological Chemistry

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Post-transcriptional mechanisms play a major role in regulating luteinizing hormone (LH) receptor mRNA expression in the ovary. An ovarian cytosolic protein that we have identified in rats and humans, which binds to a polypyrimidine-rich bipartitate sequence in the coding region of LHR mRNA, acts as a trans-acting factor in this process. In the present study, we isolated and characterized this LH receptor mRNA-binding protein (LRBP) from rat ovary. LRBP was purified to homogeneity by cation exchange chromatography followed by Northwestern analysis and subsequent elution of the single protein band from SDS-polyacrylamide gel. Purified LRBP was subjected to N-terminal microsequencing followed by homology search, which revealed its identity as mevalonate kinase. Purified rat mevalonate kinase antibody recognized the gel-purified LRBP on Western blots performed with one-and two-dimensional SDSpolyacrylamide gels. When recombinant mevalonate kinase produced in human embryonic kidney cells ( The interaction of luteinizing hormone (LH) 1 with its cell surface receptors controls reproductive functions including steroidogenesis in the gonad (1). In the ovary, luteinizing hormone receptor (LHR), a member of G s -protein coupled receptors, regulates ovarian function mainly through increased production of cAMP (2-4). The cell surface expression of LHR varies during different stages of the ovarian cycle. Its expression in granulosa cells and luteal cells is greatly decreased by an endogenous preovulatory LH surge or by the administration of a pharmacological dose of human chorionic gonadotropin (hCG), a placental counterpart of LH (5-8). We have shown that the decline in cell surface LHR expression seen after hCG administration is paralleled by a specific loss of all four LHR mRNA transcripts (6.7, 4.4, 2.6, and 1.8 kb) in the ovary (9). Furthermore, the loss of LHR mRNA does not result from decreased transcription but occurs post-transcriptionally with a 3-fold decrease in half-life (8).Regulation of mRNA turnover is one of the major control mechanisms of gene expression in all organisms. mRNA halflives are influenced by the interaction of various cytoplasmic proteins (trans-acting factors) with regulatory regions (cis-acting elements) in the mRNA, forming ribonucleoprotein (RNP) complexes (10). The formation and disruption of RNP complexes in response to various cellular stimuli mainly controls the turnover of cytoplasmic mRNA. Studies have indicated the presence of cis-acting regulatory elements in the 5Ј-untranslated region, coding region, and 3Ј-untranslated region of mRNA (10). A number of cytoplasmic trans-acting factors, some of which shuttle between the nucleus and cytoplasm, have been identified as mRNA-stabilizing, destabilizing, or translational repressor proteins (11-16). c-Fos, c-Myc, tropoelastin, thymidylate synthase, and dihydrofolate reductase are some of the mRNAs containing regulatory elements in the coding region for trans-acting factors (17-24).We have identified a LHR mRNA-binding protein in rat and hu...

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Hormonal Regulation of Luteinizing Hormone/Chorionic Gonadotropin Receptor mRNA in Rat Ovarian Cells during Follicular Development and Luteinization

Cited by 223 publications

References 53 publications

Progesterone-regulated genes in the ovulation process: ADAMTS-1 and cathepsin L proteases

Progesterone-regulated genes in the ovulation process: ADAMTS-1 and cathepsin L proteases

Gonadotropin requirements for dominant follicle selection in GnRH agonist-treated cows

Isolation and Characterization of a Novel trans-Factor for Luteinizing Hormone Receptor mRNA from Ovary

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