Recent studies have shown that bone morphogenetic proteins (BMPs) are important regulators in the pituitary–gonadal endocrine axis. We here investigated the effects of BMPs on GNRH production controlled by estrogen using murine GT1-7 hypothalamic neuron cells. GT1-7 cells expressed estrogen receptor a (ERa; ESR1 as listed in MGI Database), ERb (ESR2 as listed in MGI Database), BMP receptors, SMADs, and a binding protein follistatin. Treatment with BMP2 and BMP4 had no effect on Gnrh mRNA expression; however, BMP6 and BMP7 significantly increased Gnrh mRNA expression as well as GnRH production by GT1-7 cells. Notably, the reduction of Gnrh expression caused by estradiol (E2) was restored by cotreatment with BMP2 and BMP4, whereas it was not affected by BMP6 or BMP7. E2 activated extracellular signal-regulated kinase (ERK) 1/2 and stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK) signaling but did not activate p38-mitogenactivated protein kinase (MAPK) signaling in GT1-7 cells. Inhibition of ERK1/ERK2 reversed the inhibitory effect of estrogen on Gnrh expression, whereas SAPK/JNK inhibition did not affect the E2 actions. Expression levels of Era and Erb were reduced by BMP2 and BMP4, but were increased by BMP6 and BMP7. Treatment with an ER antagonist inhibited the E2 effects on Gnrh suppression including reduction of E2-induced ERK phosphorylation, suggesting the involvement of genomic ER actions in Gnrh suppression. BMP2 and BMP4 also suppressed estrogen-induced phosphorylation of ERK1/ERK2 and SAPK/JNK signaling, suggesting that BMP2 and BMP4 downregulate estrogen effects by attenuating ER–MAPK signaling. Considering that BMP6 and BMP7 increased the expression of a1E-subunit of R-type calcium channel (Cacna1e), which is critical for GNRH secretion, it is possible that BMP6 and BMP7 directly stimulate GNRH release by GT1-7 cells. Collectively, a newly uncovered interaction of BMPs and ER may be involved in controlling hypothalamic GNRH production and secretion via an autocrine/paracrine mechanism.
Estrogen is involved in the development and progression of breast cancer. Here, we investigated the effects of bone morphogenetic proteins (BMPs) on breast cancer cell proliferation caused by estrogen using human breast cancer MCF-7 cells.MCF-7cellsexpressestrogenreceptors(ESR1andESR2), BMP receptors, and SMAD signaling molecules. Estradiol and membrane-impermeable estradiol stimulated MCF-7 cell proliferation. Estradiol also reduced mRNA levels of ESR1, aromatase, and steroid sulfatase. Treatme...
Here we investigated roles of the pituitary bone morphogenetic protein (BMP) system in modulating GH production regulated by a somatostatin analog, octreotide (OCT) and a dopamine agonist, bromocriptine (BRC) in rat pituitary somatolactotrope tumor GH3 cells. The GH3 cells were found to express BMP ligands, including BMP-4 and BMP-6; BMP type-1 and type-2 receptors (except the type-1 receptor, activin receptor-like kinase (ALK)-6); and Smad signaling molecules. Forskolin stimulated GH production...
Last. Alan S. McNeilly(Edin.: University of Edinburgh)H-Index: 75
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We have shown previously that, in sheep primary pituitary cells, bone morphogenetic proteins (BMP)-4 inhibits FSHb mRNA expression and FSH release. In contrast, in mouse LbT2 gonadotrophs, others have shown a stimulatoryeffect of BMPs on basal or activin-stimulated FSHb promoter-driven transcription. As a species comparison with our previous results, we used LbT2 cells to investigate the effects of BMP-4 on gonadotrophin mRNA and secretion modulated by activin and GnRH. BMP-4 alone had no effect...
Progenitor cells that express the transcription factor olig1 generate several neural cell types including oligodendrocytes and GABAergic interneurons in the dorsal cortex. The fate of these progenitor cells is regulated by a number of signals including bone morphogenetic proteins (BMPs) secreted in the dorsal forebrain. BMPs signal by binding to heteromeric serine–threonine kinase receptors formed by type I (BMPR1a, BMPR1b, Alk2) and type II (BMPRII) subunits. To determine the specific role of t...
Involvement of peroxisome proliferator-activated receptor-g (PPAR-g) activation and bone morphogenetic protein (BMP) signaling in regulating cell proliferation and hormonal production of pituitary tumors has been reported, although the underlying mechanism remains poorly understood. Here, we investigated regulatory roles of PPARa and PPARg in gonadotropin transcription and cell mitosis modulated by pituitary activin/BMP systems using a mouse gonadotropinoma cell line LbT2, which expresses activi...
Aldosterone and angiotensin II (ANG II) contribute to the development and progression of renal damage. Here we investigated the effects of bone morphogenetic proteins (BMPs) on renal cell proliferation evoked by aldosterone and ANG II with mouse mesangial cells, which express mineralocorticoid receptors (MR), ANG II type 1 receptors, and BMP signaling molecules. Aldosterone and ANG II stimulated mesangial cell mitosis and activated ERK1/2 and SAPK/JNK signaling. These aldosterone effects were ne...
Aldosterone production is modified by several growth factors that reside in the adrenal. We have recently reported the existence of a bone morphogenetic protein (BMP) system in human adrenocortical cells, in which BMP-6 augments aldosterone synthesis. Here, we investigated functional roles of BMP-6, focusing on the differential regulation of aldosterone synthesis induced by angiotensin (Ang) II and potassium (K). In human adrenocortical H295R cells, BMP-6 augmented Ang II-induced CYP11B2 transcr...
Bone morphogenetic proteins (BMPs) play critical roles in folliculogenesis by modulating the actions of follicle-stimulating hormone (FSH) in the ovary. However, the effects of FSH on the BMP system remain unknown. Here, we have investigated the effects of FSH on BMP signaling using the human granulosa-like tumor cell line KGN. KGN cells express BMP type I and type II receptors and the BMP signaling molecules SMADs. FSH administration upregulated BMP type IA (BMPR1A) and IB (BMPR1B) receptors, a...
#2Mario Díaz(ULL: University of La Laguna)H-Index: 27
Last. Rafael Alonso(ULL: University of La Laguna)H-Index: 22
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Hypothalamic luteinizing hormone-releasing hormone neurons (LHRH) form the final pathway for the central control of reproduction through the release of LHRH into the pituitary-hypothalamic system. We previously found that LHRH-producing GT1-7 cells respond to acetylcholine (ACh) with an increase in intracellular calcium ([Ca 2 + ] ι ) through activation of muscarinic receptors. This effect is acutely modulated by 17β-estradiol in a manner compatible with specific membrane binding sites. Because ...
#1Richard J. Pietras(UCLA: University of California, Los Angeles)H-Index: 52
#2Ellis R. Levin(UCI: University of California, Irvine)H-Index: 69
Last. Clara M. Szego(UCLA: University of California, Los Angeles)H-Index: 32
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The Report by C. M. Revankar et al. (“A transmembrane intracellular estrogen receptor mediates rapid cell signaling,” 11 Mar., p. 1625) presents findings that the G protein-coupled receptor GPR30 localizes exclusively to endoplasmic reticulum and binds an estradiol-Alexa dye conjugate. As such,
Prenatal high-fat diet exposure increases hypothalamic neurogenesis events in embryos and programs offspring to be obesity-prone. The molecular mechanism involved in these dietary effects of neurogenesis are unknown. This study investigated the effects of oleic and palmitic acids, which are abundant in a high-fat diet, on the hypothalamic neuronal transcriptome and how these changes impact neurogenesis events. The results show differential effects of low and high concentrations of oleic or palmi...
Last. Angela M. Mabb(GSU: Georgia State University)H-Index: 17
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RNF216/TRIAD3 is an E3 ligase that ubiquitinates substrates in the nervous system. Recessive mutations in RNF216/TRIAD3 cause Gordon Holmes syndrome (GHS), where hypogonadotropic hypogonadism is a core phenotype. However, the functions of RNF216/TRIAD3 within the neuroendocrine system are not well-understood. Here, we used the CRISPR-Cas9 system to knock out Rnf216/Triad3 in GT1-7 cells, a GnRH immortalized cell line derived from mouse hypothalamus. Rnf216/Triad3 knockout cells had decreased ste...
Abstract Nickel (Ni) is a ubiquitous environmental pollutant, which can disrupt the production of steroid in rat Leydig cells. Steroidogenesis can be affected by non-coding RNAs (ncRNAs), which operate in normal physiological processes. To date, however, very few studies have focused on whether ncRNAs are involved in Ni-induced steroidogenesis disturbance. The present study was designed to investigate the impact of NiSO4 on the regulation of RNA networks including long non-coding RNA (lncRNA), m...
#2Santiago Elías Charif(CONICET: National Scientific and Technical Research Council)H-Index: 4
Last. Verónica Berta Dorfman(CONICET: National Scientific and Technical Research Council)H-Index: 5
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Abstract The South American plains vizcacha, Lagostomus maximus, is the only mammal described so far that shows expression of estrogen receptors (ERs) and progesterone receptors (PRs) in gonadotropin-releasing hormone (GnRH) neurons. This animal therefore constitutes an exceptional model for the study of the effect of steroid hormones on the modulation of the hypothalamic-pituitary-ovarian (HPO) axis. By using both in vivo and ex vivo approaches, we have found that pharmacological doses of proge...
To evaluate the effects of Huang Bai (Phellodendron amurense) on growth and maturation in adolescent female rats. Female Sprague–Dawley rats (28 days old; n = 72) were divided into six daily treatment groups: control (distilled water), Huang Bai (100 and 300 mg/kg), recombinant human GH (rhGH; 20 μg/kg), estradiol (1 μg/kg), and triptorelin (100 μg). Body weight, food intake, and vaginal opening were measured daily from postnatal day (PND) 28 to PND 43. Tetracycline (20 mg/kg) was injected on PN...
Recent studies have shown that N-carbamylglutamate (NCG) and arginine (ARG) supplementation improves reproductive performance in livestock. The objectives of the present study were to evaluate the effects of NCG and ARG on GT1-7 cell gonadotrophin-releasing hormone (GnRH) secretion, gene expression and cell proliferation. GT1-7 cells were treated in vitro with different concentrations of NCG (0–1.0 mM) or ARG (0–4.0 mM) in serum-free medium for 12 or 24 h. For GnRH secretion and cell proliferati...
Last. Marilina Casais(Instituto de Biología y Medicina Experimental)H-Index: 1
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Abstract The aim of this work was to investigate if noradrenaline (NA), added in the coeliac ganglion –superior ovarian nerve- ovary system (CG-SON-O) and in ovary incubation, modifies the release of ovarian progesterone (P 4 ), gonadotropin-releasing hormone ( GnRH) and oestradiol (E 2 ), and the expression of 3β-HSD and 20α-HSD and proapoptotic bax and antiapoptotic bcl-2 on dioestrus II in the rat. The CG-SON-O system and the ovary were removed and placed in one cuvette containing Krebs–Ringe...
#2Jung Hoon Kang(NIH: National Institutes of Health)H-Index: 2
Last. James H. Segars(NIH: National Institutes of Health)H-Index: 57
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17β-estradiol (E2), a key participant on the initiation of the LH surge, exerts both positive and negative feedback on GnRH neurons. We sought to investigate potential interactions between estrogen receptors alpha (ERα) and beta (ERβ) and gonadotropin releasing hormone receptor (GnRH-R) in GT1-7 cells. Radioligand binding studies demonstrated a significant decrease in saturation E2 binding in cells treated with GnRH agonist. Conversely, there was a significant reduction in GnRH binding in GT1-7 ...
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 wi...
#1Masaya Takeda(UCSD: University of California, San Diego)H-Index: 1
#1Masaya Takeda(UCSD: University of California, San Diego)H-Index: 19
Last. Mark A. Lawson(UCSD: University of California, San Diego)H-Index: 25
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It is known that bone morphogenetic proteins (BMPs) regulate gonadotropin transcription and production by pituitary gonadotrope cells. However, the role of BMPs in gonadotropin-releasing hormone (GnRH)-induced FSH production remains uncertain. Here, we describe a functional link between BMP-6 and BMP-7 signals and FSH transcriptional activity induced by GnRH using mouse gonadotrope LβT2 cells. In LβT2 cells, BMP-6 and BMP-7 increased mouse FSHβ-promoter activity in a concentration-dependent mann...