LH-Receptor Gene Expression in Human Granulosa and Cumulus Cells from Antral and Preovulatory Follicles

Jeppesen, Janni Vikkelsø; Kristensen, Stine Gry; Nielsen, M.E.; Humaıdan, Peter; Canto, Maria Dal; Fadini, Rubens; Schmidt, Kirsten Tryde; Ernst, Erik; Andersen, Claus Yding

doi:10.1210/jc.2012-1427

Cited by 195 publications

(145 citation statements)

References 34 publications

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“…Consistent with other authors, LHR density in the present study was accelerated in the pre-ovulatory follicle in the WT and the BB, and it was followed by a significant reduction in the leading dominant follicle of each animal (Figs 6C and 7C;LaPolt et al 1992, Jeppesen et al 2012, Ophir et al 2014.…”

Section: Steroidogenic Differentiation and Lhr Earlier Acquisitionsupporting

confidence: 93%

Flow cytometric analysis of FSHR, BMRR1B, LHR and apoptosis in granulosa cells and ovulation rate in merino sheep

Regan¹,

McFarlane²,

O’Shea³

et al. 2015

Reproduction

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The aim of the present study was to determine the direct cause of the mutation-induced, increased ovulation rate in Booroola Merino (BB) sheep. Granulosa cells were removed from antral follicles before ovulation and post-ovulation from BB (nZ5) and WT (nZ12) Merino ewes. Direct immunofluorescence measurement of mature cell surface receptors using flow cytometry demonstrated a significant up-regulation of FSH receptor (FSHR), transforming growth factor beta type 1, bone morphogenetic protein receptor (BMPR1B), and LH receptor (LHR) in BB sheep. The increased density of FSHR and LHR provide novel evidence of a mechanism for increasing the number of follicles that are recruited during dominant follicle selection. The compounding increase in receptors with increasing follicle size maintained the multiple follicles and reduced the apoptosis, which contributed to a high ovulation rate in BB sheep. In addition, we report a mutation-independent mechanism of down-regulation to reduce receptor density of the leading dominant follicle in sheep. The suppression of receptor density coincides with the cessation of mitogenic growth and steroidogenic differentiation as part of the luteinization of the follicle. The BB mutation-induced attenuation of BMPR1B signaling led to an increased density of the FSHR and LHR and a concurrent reduction in apoptosis to increase the ovulation rate. The role of BMPs in receptor modulation is implicated in the development of multiple ovulations.Reproduction (2015) 150 151-163

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Section: Steroidogenic Differentiation and Lhr Earlier Acquisitionsupporting

confidence: 93%

Flow cytometric analysis of FSHR, BMRR1B, LHR and apoptosis in granulosa cells and ovulation rate in merino sheep

Regan¹,

McFarlane²,

O’Shea³

et al. 2015

Reproduction

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show abstract

“…A likely explanation for this result is that here investigated GCs were exposed to hCG in vivo. As shown by us and others (Murphy 2000, Hurwitz et al 2010, Jeppesen et al 2012, McReynolds et al 2012, hCG administration causes luteinization of GCs, and a changing physiological and molecular signatures. Therefore, it is possible that hCG administration changes cell sensitivity of the FSH response.…”

Section: Discussionmentioning

confidence: 76%

“…Increased PGR (Natraj & Richards 1993) and CYP11A1 (Rao et al 1978) expression has been reported in rat luteinized GCs. Studies in humans and in the bovine suggest that LH surge-induced declines of FSHR represent the initiation of GC luteinization (Nimz et al 2009, Jeppesen et al 2012. Likewise, disappearance of CYP19A1 is another marker of luteinization in GCs (Campbell et al 1998).…”

Section: Discussionmentioning

confidence: 99%

Aging-related premature luteinization of granulosa cells is avoided by early oocyte retrieval

Wu¹,

Barad²,

Kushnir³

et al. 2015

Journal of Endocrinology

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Why IVF pregnancy rates decline sharply after age 43 is unknown. In this study, we compared granulosa cell (GC) function in young oocyte donors (nZ31, ages 21-29), middle-aged (nZ64, ages 30-37) and older infertile patients (nZ41, ages 43-47). Gene expressions related to gonadotropin activity, steroidogenesis, apoptosis and luteinization were examined by real-time PCR and western blot in GCs collected from follicular fluid. FSH receptor (FSHR), aromatase (CYP19A1) and 17b-hydroxysteroid dehydrogenase (HSD17B) expression were found down regulated with advancing age, while LH receptor (LHCGR), P450scc (CYP11A1) and progesterone receptor (PGR) were up regulated. Upon in vitro culture, GCs were found to exhibit lower proliferation and increased apoptosis with aging. While FSH supplementation stimulated GCs growth and prevented luteinization in vitro. These observations demonstrate age-related functional declines in GCs, consistent with premature luteinization. To avoid premature luteinization in women above age 43, we advanced oocyte retrieval by administering human chorionic gonadotropin at maximal leading follicle size of 16 mm (routine 19-21 mm). Compared to normal cycles in women of similar age, earlier retrieved patients demonstrated only a marginal increase in oocyte prematurity, yet exhibited improved embryo numbers as well as quality and respectable clinical pregnancy rates. Premature follicular luteinization appears to contribute to rapidly declining IVF pregnancy chances after age 43, and can be avoided by earlier oocyte retrieval.

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“…675 Furthermore, healthy follicles at late stages of maturation in human ovaries are described to possess significant AR immunoreactivity. 625,678,679 A recent report has suggested that AR expression is highest in small antral follicles and decreases as the follicle matures, 685 suggesting that message levels may not correspond with AR protein levels in human follicles.…”

Section: Ar Expression In the Ovarymentioning

confidence: 99%

Steroid Receptors in the Uterus and Ovary

Binder

Winuthayanon

Hewitt

et al. 2015

Knobil and Neill's Physiology of Reproduction

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LH-Receptor Gene Expression in Human Granulosa and Cumulus Cells from Antral and Preovulatory Follicles

Cited by 195 publications

References 34 publications

Flow cytometric analysis of FSHR, BMRR1B, LHR and apoptosis in granulosa cells and ovulation rate in merino sheep

Flow cytometric analysis of FSHR, BMRR1B, LHR and apoptosis in granulosa cells and ovulation rate in merino sheep

Aging-related premature luteinization of granulosa cells is avoided by early oocyte retrieval

Steroid Receptors in the Uterus and Ovary

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