RESUMEN
A growing body of literature provides evidence of a prominent role for bone morphogenetic proteins (BMPs) in regulating various stages of ovarian follicle development. Several actions for BMP6 have been previously reported in the hen ovary, yet only within postselection (preovulatory) follicles. The initial hypothesis tested herein is that BMP6 increases FSH receptor (FSHR) mRNA expression within the granulosa layer of prehierarchal (6-8âmm) follicles (6-8 GC). BMP6 mRNA is expressed at higher levels within undifferentiated (1-8âmm) follicles compared with selected (≥9âmm) follicles. Recombinant human (rh) BMP6 initiates SMAD1, 5, 8 signaling in cultured 6-8âGC and promotes FSHR mRNA expression in a dose-related fashion. In addition, a 21âh preculture with rhBMP6 followed by a 3âh challenge with FSH increases cAMP accumulation, STAR (StAR) expression, and progesterone production. Interestingly, rhBMP6 also increases expression of anti-Müllerian hormone (AMH) mRNA in cultured 6-8âGC. This related BMP family member has previously been implicated in negatively regulating FSH responsiveness during follicle development. Considering these data, we propose that among the paracrine and/or autocrine actions of BMP6 within prehierarchal follicles is the maintenance of both FSHR and AMH mRNA expression. We predict that before follicle selection, one action of AMH within granulosa cells from 6 to 8âmm follicles is to help suppress FSHR signaling and prevent premature granulosa cell differentiation. At the time of selection, we speculate that the yet undefined signal directly responsible for selection initiates FSH responsiveness. As a result, FSH signaling suppresses AMH expression and initiates the differentiation of granulosa within the selected follicle.
Asunto(s)
Hormona Antimülleriana/genética , Proteína Morfogenética Ósea 6/farmacología , Pollos , Células de la Granulosa/efectos de los fármacos , Folículo Ovárico/efectos de los fármacos , Receptores de HFE/genética , Animales , Hormona Antimülleriana/metabolismo , Proteína Morfogenética Ósea 6/genética , Proteína Morfogenética Ósea 6/metabolismo , Proteína Morfogenética Ósea 6/fisiología , Pollos/genética , Pollos/metabolismo , Pollos/fisiología , Relación Dosis-Respuesta a Droga , Femenino , Hormona Folículo Estimulante/farmacología , Expresión Génica/efectos de los fármacos , Células de la Granulosa/metabolismo , Células de la Granulosa/fisiología , Humanos , Oogénesis/efectos de los fármacos , Oogénesis/genética , Oogénesis/fisiología , Folículo Ovárico/citología , Folículo Ovárico/metabolismo , Folículo Ovárico/fisiología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores de HFE/metabolismo , Proteínas Recombinantes/farmacología , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Gonadotrophin-inhibitory hormone (GnIH), a hypothalamic RFamide, has been found to inhibit gonadotrophin secretion from the anterior pituitary gland originally in birds and, subsequently, in mammalian species. The gene encoding a transmembrane receptor for GnIH (GnIHR) was recently identified in the brain, pituitary gland and gonads of song bird, chicken and Japanese quail. The objectives of the present study are to characterise the expression of GnIHR mRNA and protein in the chicken pituitary gland, and to determine whether sexual maturation and gonadal steroids influence pituitary GnIHR mRNA abundance. GnIHR mRNA quantity was found to be significantly higher in diencephalon compared to either anterior pituitary gland or ovaries. GnIHR mRNA quantity was significantly higher in the pituitaries of sexually immature chickens relative to sexually mature chickens. Oestradiol or a combination of oestradiol and progesterone treatment caused a significant decrease in pituitary GnIHR mRNA quantity relative to vehicle controls. GnIHR-immunoreactive (ir) cells were identified in the chicken pituitary gland cephalic and caudal lobes. Furthermore, GnIHR-ir cells were found to be colocalised with luteinising hormone (LH)beta mRNA-, or follicle-stimulating hormone (FSH)beta mRNA-containing cells. GnIH treatment significantly decreased LH release from anterior pituitary gland slices collected from sexually immature, but not from sexually mature chickens. Taken together, GnIHR gene expression is possibly down regulated in response to a surge in circulating oestradiol and progesterone levels as the chicken undergoes sexual maturation to allow gonadotrophin secretion. Furthermore, GnIHR protein expressed in FSHbeta or LHbeta mRNA-containing cells is likely to mediate the inhibitory effect of GnIH on LH and FSH secretion.
