Heifers express G-protein coupled receptor 61 in anterior pituitary gonadotrophs in stage-dependent manner

Pandey, Kiran; Kereilwe, Onalenna; Borromeo, V.; Kadokawa, Hiroya

doi:10.1016/j.anireprosci.2017.03.020

Cited by 11 publications

(17 citation statements)

References 45 publications

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“…6c) colocalize with GnRHRs in the limited area of the plasma membrane in bovine gonadotrophs. The positive overlap coefficient calculated by confocal data analysis software was very strong (more than 0.70) between GnRHR and GPR61, between GnRHR and GPR153, and between GnRHR and AMHR2 on the cell-surface of gonadotrophs [33][34][35].…”

Section: Colocalization Of Gpr61 Gpr153 and Amhr2 With Gnrhr In Thementioning

confidence: 94%

“…Therefore, I speculated that GPR61, GPR153, and AMHR2 might colocalize with GnRHR in the limited area of the plasma membrane of gonadotrophs. To test this hypothesis, I examined the colocalization of GnRHR with each one of these receptors (and with either the LHβ subunit or FSHβ subunit) in both AP tissue and cultured AP cells using immunofluorescence microscopy [33][34][35]. I found that GPR61 (Fig.…”

Section: Colocalization Of Gpr61 Gpr153 and Amhr2 With Gnrhr In Thementioning

confidence: 99%

“…To further the current understanding of GnRHR, I developed an antibody targeting the N-terminus of the extracellular domain of GnRHR for immunohistochemistry, fluorescence-activated cell sorting, and immunocytochemistry assays [ 32 ]. Bovine GnRHRs are aggregated and restricted to a limited area of the cell surface (rather than evenly dispersed) of LH-monohormonal, FSH-monohormonal, and bihormonal gonadotrophs [ 32 , 33 , 34 , 35 ] ( Fig. 3

Fig.…”

Section: Gnrh Receptors Localization In the Limited Area Of Plasma Mementioning

confidence: 99%

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Discovery of new receptors regulating luteinizing hormone and follicle-stimulating hormone secretion by bovine gonadotrophs to explore a new paradigm for mechanisms regulating reproduction

Kadokawa

2020

J. Reprod. Dev.

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Previous studies in the 1960s and 1970s have reported that both gonadotropin-releasing hormone (GnRH) and estradiol-activated nuclear estrogen receptors regulate gonadotropin secretion in women. However, I had previously reported that gonadotroph function is regulated by complex crosstalk between several membrane receptors. RNA-seq had previously revealed 259 different receptor genes expressed in the anterior pituitary of heifers. However, the biological roles of most of these receptors remain unknown. I identified four new receptors of interest: G protein-coupled receptor 30 (GPR30), anti-Mullerian hormone (AMH) receptor type 2 (AMHR2), and G protein-coupled receptors 61 and 153 (GPR61 and GPR153). GPR30 rapidly (within a few minutes) mediates picomolar, but not nanomolar, levels of estradiol to suppress GnRH-induced luteinizing hormone (LH) secretion from bovine gonadotrophs, without decreasing mRNA expressions of the LHα, LHβ, or follicle-stimulating hormone (FSH) β subunits. GPR30 is activated by other endogenous estrogens, estrone and estriol. Moreover, GPR30 activation by zearalenone, a nonsteroidal mycoestrogen, suppresses LH secretion. AMHR2, activated by AMH, stimulates LH and FSH secretion, thus regulating gonadotrophs, where other TGF-β family members, including inhibin and activin, potentially affect FSH secretion. I also show that GPR61, activated by its ligand (recently discovered) significantly alters LH and FSH secretion. GPR61, GPR153, and AMHR2 colocalize with the GnRH receptor in unevenly dispersed areas of the bovine gonadotroph cell surface, probably lipid rafts. The findings summarized in this review reveal a new paradigm regarding the mechanisms regulating reproduction via novel receptors expressed on bovine gonadotrophs.

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Section: Colocalization Of Gpr61 Gpr153 and Amhr2 With Gnrhr In Thementioning

confidence: 94%

Section: Colocalization Of Gpr61 Gpr153 and Amhr2 With Gnrhr In Thementioning

confidence: 99%

Fig.…”

Section: Gnrh Receptors Localization In the Limited Area Of Plasma Mementioning

confidence: 99%

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Discovery of new receptors regulating luteinizing hormone and follicle-stimulating hormone secretion by bovine gonadotrophs to explore a new paradigm for mechanisms regulating reproduction

Kadokawa

2020

J. Reprod. Dev.

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“…The lipid rafts are distinct, relatively insoluble regions that have lower density and are less fluid than surrounding membrane (Simons et al 2000;Head et al 2014), and they facilitate signaling by allowing colocalization of membrane receptors and their downstream signaling components (Simons et al 2000;Head et al 2014). We recently discovered that two orphan receptors, GPR61 and GPR153, are colocalized with GnRHR in gonadotroph plasma membrane lipid rafts (Pandey et al 2017a(Pandey et al , 2017b. Therefore, gonadotroph lipid rafts containing GnRHR may contain AMHR2.…”

Section: Introductionmentioning

confidence: 99%

Anti-Müllerian hormone receptor type 2 is expressed in gonadotrophs of postpubertal heifers to control gonadotrophin secretion

Kereilwe

Pandey

Borromeo

et al. 2018

Reprod. Fertil. Dev.

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Preantral and small antral follicles may secret anti-Müllerian hormone (AMH) to control gonadotrophin secretion from ruminant gonadotrophs. The present study investigated whether the main receptor for AMH, AMH receptor type 2 (AMHR2), is expressed in gonadotrophs of postpubertal heifers to control gonadotrophin secretion. Expression of AMHR2 mRNA was detected in anterior pituitaries (APs) of postpubertal heifers using reverse transcription-polymerase chain reaction. An anti-AMHR2 chicken antibody was developed against the extracellular region near the N-terminus of bovine AMHR2. Western blotting using this antibody detected the expression of AMHR2 protein in APs. Immunofluorescence microscopy using the same antibody visualised colocalisation of AMHR2 with gonadotrophin-releasing hormone (GnRH) receptor on the plasma membrane of gonadotrophs. AP cells were cultured for 3.5 days and then treated with increasing concentrations (0, 1, 10, 100, or 1000pgmL-1) of AMH. AMH (10-1000pgmL-1) stimulated (P<0.05) basal FSH secretion. In addition, AMH (100-1000pgmL-1) weakly stimulated (P<0.05) basal LH secretion. AMH (100-1000pgmL-1) inhibited GnRH-induced FSH secretion, but not GnRH-induced LH secretion, in AP cells. In conclusion, AMHR2 is expressed in gonadotrophs of postpubertal heifers to control gonadotrophin secretion.

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“…We used also a specific guinea pig polyclonal anti-bovine GnRHR (Kadokawa et al 2014), a specific mouse monoclonal anti-LH β (LHβ) subunit antibody (clone 518-B7; Matteri et al 1987;Iqbal et al 2009), and a specific mouse monoclonal anti-FSH β (FSHβ) subunit antibody (clone A3C12; Borromeo et al 2004) for immunohistochemical analysis of AP tissue. These antibodies are utilized for immunohistochemical analysis of AP tissue in our previous papers (Kadokawa et al 2014;Pandey et al 2017aPandey et al , 2017bKereilwe et al 2018) Western Blotting for AMH detection Proteins were extracted from the AP (n = 4) or ovary samples (n = 4, used as positive controls) and western blotting was performed as previously described (Kereilwe et al 2018). The extracted protein sample (33.4µg of total protein in 37.5µl) was mixed in…”

Section: Antibodies Used In This Studymentioning

confidence: 99%

Bovine gonadotrophs express anti-Müllerian hormone (AMH): comparison of AMH mRNA and protein expression levels between old Holsteins and young and old Japanese Black females

Kereilwe

Kadokawa

2019

Reprod. Fertil. Dev.

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Anti-Müllerian hormone (AMH) is secreted from ovaries and stimulates gonadotrophin secretion from bovine gonadotroph cells. Other important hormones for endocrinological gonadotroph regulation (e.g. gonadotrophin-releasing hormone, inhibin and activin) have paracrine and autocrine roles. Therefore, in this study, AMH expression in bovine gonadotroph cells and the relationships between AMH expression in the bovine anterior pituitary (AP) and oestrous stage, age and breed were evaluated. AMH mRNA expression was detected in APs of postpubertal heifers (26 months old) by reverse transcription-polymerase chain reaction. Based on western blotting using an antibody to mature C-terminal AMH, AMH protein expression was detected in APs. Immunofluorescence microscopy utilising the same antibody indicated that AMH is expressed in gonadotrophs. The expression of AMH mRNA and protein in APs did not differ between oestrous phases (P>0.1). We compared expression levels between old Holsteins (79.2±10.3 months old) and young (25.9±0.6 months old) and old Japanese Black females (89.7±20.3 months old). The APs of old Holsteins exhibited lower AMH mRNA levels (P<0.05) but higher AMH protein levels than those of young Japanese Black females (P<0.05). In conclusion, bovine gonadotrophs express AMH and this AMH expression may be breed-dependent.

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Heifers express G-protein coupled receptor 61 in anterior pituitary gonadotrophs in stage-dependent manner

Cited by 11 publications

References 45 publications

Discovery of new receptors regulating luteinizing hormone and follicle-stimulating hormone secretion by bovine gonadotrophs to explore a new paradigm for mechanisms regulating reproduction

Discovery of new receptors regulating luteinizing hormone and follicle-stimulating hormone secretion by bovine gonadotrophs to explore a new paradigm for mechanisms regulating reproduction

Anti-Müllerian hormone receptor type 2 is expressed in gonadotrophs of postpubertal heifers to control gonadotrophin secretion

Bovine gonadotrophs express anti-Müllerian hormone (AMH): comparison of AMH mRNA and protein expression levels between old Holsteins and young and old Japanese Black females

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