Interaction between gonadotropin-releasing hormone and bone morphogenetic protein-6 and -7 signaling in LβT2 gonadotrope cells

Takeda, Masaya; Otsuka, Fumio; Takahashi, Hiroaki; Inagaki, Kenichi; Miyoshi, Tomoko; Tsukamoto, Naoko; Makino, Hírofumi; Lawson, Mark A.

doi:10.1016/j.mce.2011.08.001

Cited by 17 publications

(9 citation statements)

References 32 publications

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“…The BMP signaling axis has been strongly associated with the gonadotropins FSH and LH in the pituitary-ovarian axis of control in the regulation of follicle recruitment, growth, and ovulation rate (Otsuka et al 2001a, Miyoshi et al 2006, Takeda et al 2012. The BMP ligands 4, 6, 7, and 15 have been shown to have a stage-dependent high affinity to bind to the TGFb type 1 receptor BMPR1B (Mazerbourg & Hsueh 2006).…”

Section: Discussionmentioning

confidence: 99%

“…It is therefore apparent that the down-regulation mechanism is independent of the mutation, seeing as it occurred in both genotypes. The BMPs 4, 6, 7, and 15 signal via the BMPR1B, and they have been previously shown to play a regulatory role in the suppression of progesterone production before ovulation (Ryan et al 2008, Takeda et al 2012. The up-regulation of ERK1/2 signaling (Fan et al 2009) occurs coincident with the down-regulation of BMPR1B activity, which suppresses progesterone synthesis (Miyoshi et al 2006, Feary et al 2007.…”

Section: Pattern Of Biphasic Down-regulation In Wt Sheepmentioning

confidence: 99%

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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: Discussionmentioning

confidence: 99%

Section: Pattern Of Biphasic Down-regulation In Wt Sheepmentioning

confidence: 99%

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 BMP system has been shown to play critical roles in initial development of the anterior pituitary (Scully and Rosenfeld, 2002), and BMPs modulate GnRH responses in gonadotropes (Takeda et al, 2012). BMP-4 is necessary for the first step of pituitary organogenesis including the proliferation of Rathke’s pouch, which gives rise to Pit-1 lineage cells.…”

Section: Discussionmentioning

confidence: 99%

Mutual interaction of kisspeptin, estrogen and bone morphogenetic protein-4 activity in GnRH regulation by GT1-7 cells

Terasaka

Otsuka

Tsukamoto

et al. 2013

Molecular and Cellular Endocrinology

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Reproduction is integrated by interaction of neural and hormonal signals converging on hypothalamic neurons for controlling gonadotropin-releasing hormone (GnRH). Kisspeptin, the peptide product of the kiss1 gene and the endogenous agonist for the GRP54 receptor, plays a key role in the regulation of GnRH secretion. In the present study, we investigated the interaction between kisspeptin, estrogen and BMPs in the regulation of GnRH production by using mouse hypothalamic GT1-7 cells. Treatment with kisspeptin increased GnRH mRNA expression and GnRH protein production in a concentrationdependent manner. The expression levels of kiss1 and GPR54 were not changed by kisspeptin stimulation. Kisspeptin induction of GnRH was suppressed by co-treatment with BMPs, with BMP-4 action being the most potent for suppressing the kisspeptin effect. The expression of kisspeptin receptor, GPR54, was suppressed by BMPs, and this effect was reversed in the presence of kisspeptin. It was also revealed that BMP-induced Smad1/5/8 phosphorylation and Id-1 expression were suppressed and inhibitory Smad6/7 was induced by kisspeptin. In addition, estrogen induced GPR54 expression, while kisspeptin increased the expression levels of ERα and ERβ, suggesting that the actions of estrogen and kisspeptin are mutually enhanced in GT1-7 cells. Moreover, kisspeptin stimulated MAPKs and AKT signaling, and ERK signaling was functionally involved in the kisspeptin-induced GnRH expression. BMP-4 was found to suppress kisspeptin-induced GnRH expression by reducing ERK signaling activity. Collectively, the results indicate that the axis of kisspeptin-induced GnRH production is bi-directionally controlled, being augmented by an interaction between ERα/β and GPR54 signaling and suppressed by BMP-4 action in GT1-7 neuron cells.

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“…Therefore, and since the expression of BMP members changes throughout a menstrual cycle, it seems that the relationship between GH/IGF-1 and BMP signal intensities, and that the type of them, plays a key role in the regulation of Gns-dependent steroidogenesis in follicles. Moreover, BMP also participate in the regulation of the hypothalamic secretion of GnRH and ovarian sensitivity to Gns (62). These effects of BMP, particularly BMP-15, have been also seen in humans (63, 64).…”

Section: Ovarian Functioningmentioning

confidence: 99%

The Role of Growth Hormone on Ovarian Functioning and Ovarian Angiogenesis

Devesa¹,

Caicedo

2019

Front. Endocrinol.

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Although not yet well-understood, today it is clear that Growth Hormone (GH) exerts a relevant role in the regulation of ovulation and fertility; in fact, fertility is lower in women with GH deficiency (GHD), and GH receptors (GHR) and GH mRNA have been found in the ovary since the onset of follicular development in humans. However, despite the strong evidence of GH in the regulation of fertility, many aspects of GH actions at this level are still not well-established, and it is likely that some controversial data depend on the species analyzed, the dose of the hormone and the duration of use of GH. Folliculogenesis, ovulation, and corpus luteum formation and maintenance are processes that are critically dependent on angiogenesis. In the ovary, new blood vessel formation facilitates oxygen, nutrients, and hormone substrate delivery, and also secures transfer of different hormones to targeted cells. Some growth factors and hormones overlap their actions in order to control the angiogenic process for fertility. However, we still know very little about the factors that play a critical role in the vascular changes that occur during folliculogenesis or luteal regression. To promote and maintain the production of VEGF-A in granulosa cells, the effects of local factors such as IGF-I and steroids are needed; that VEGF-A-inducing effect cannot be induced by luteinizing hormone (LH) or chorionic gonadotropin (CG) alone. As a result of the influences that GH exerts on the hypothalamic-pituitary-gonadal axis, facilitating the release of gonadotropins, and given the relationship between GH and local ovarian factors such as VEGF-A, FGF-2, IGF-1, or production of sex steroids, we assume that GH has to be a necessary factor in ovarian angiogenesis, as it happens in other vascular beds. In this review we will discuss the actions of GH in the ovary, most of them likely due to the local production of the hormone and its mediators.

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Interaction between gonadotropin-releasing hormone and bone morphogenetic protein-6 and -7 signaling in LβT2 gonadotrope cells

Cited by 17 publications

References 32 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

Mutual interaction of kisspeptin, estrogen and bone morphogenetic protein-4 activity in GnRH regulation by GT1-7 cells

The Role of Growth Hormone on Ovarian Functioning and Ovarian Angiogenesis

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