Immunolocalization of Ghrelin and Its Functional Receptor, the Type 1a Growth Hormone Secretagogue Receptor, in the Cyclic Human Ovary

Abstract

Ghrelin is a novel 28-amino acid peptide identified as the endogenous ligand for the GH secretagogue receptor (GHS-R). Besides its hallmark central neuroendocrine effects in the control of GH secretion and food intake, an unexpected reproductive facet of ghrelin has recently emerged because expression of this molecule and its cognate receptor has been demonstrated in rat testis. However, whether this signaling system is present in human gonads remains to be evaluated. In this study, we have assessed the presence and cellular location of ghrelin and its functional receptor, namely the type 1a GHS-R, in the cyclic human ovary by means of immunohistochemistry using specific polyclonal antibodies. Strong ghrelin immunostaining was demonstrated in ovarian hilus interstitial cells. In contrast, ghrelin signal was not detected in ovarian follicles at any developmental stage, nor was it present in newly formed corpora lutea (CL) at very early development. However, specific ghrelin immunoreactivity was clearly observed in young and mature CL, whereas expression of the peptide disappeared in regressing luteal tissue. Concerning the cognate receptor, ovarian expression of GHS-R1a protein showed a wider pattern of tissue distribution, with detectable specific signal in oocytes as well as somatic follicular cells; luteal cells from young, mature, old, and regressing CL; and interstitial hilus cells. Of particular note, follicular GHS-R1a peptide expression paralleled follicle development with stronger immunostaining in granulosa and theca layers of healthy antral follicles. In conclusion, our results are the first to demonstrate that ghrelin and its functional type 1a receptor are expressed in the cyclic human ovary with distinct patterns of cellular location. The presence of both components (ligand and receptor) of the ghrelin signaling system within the human ovary opens up the possibility of a potential regulatory role of this novel molecule in ovarian function under physiological and pathophysiological conditions.

Ghrelin as a novel locally produced relaxing peptide of the iris sphincter and dilator muscles

“…This receptor is also expressed in thyroid gland, pancreas, spleen, adrenal gland, heart, rat testis, ovary and prostate cancer cells Iglesias et al, 2004;Gnanapavan et al, 2002;Tena-Sempere et al, 2002;Jeffery et al, 2002;Gaytan et al, 2003). In the heart, the negative inotropic effect of ghrelin has been shown, however, to be independent of GHSR-1a (Bedendi et al, 2003;Sharif et al, 2004).…”

Rosiglitazone treatment increases plasma levels of adiponectin and decreases levels of resistin in overweight women with PCOS: a randomized placebo-controlled study

“…It has been suggested to be an important regulatory peptide in food intake, long-term body weight regulation, glucose metabolism and ovarian function (39,40). Low serum ghrelin levels have been shown to be associated with abdominal obesity, hyperinsulinaemia and insulin resistance in type 2 diabetic patients (41,42) and to be decreased in women with PCOS (43).…”

Efecto de la gastrectomía tubular vertical en los niveles de ghrelina plasmática en pacientes obesos

“…No tenemos una explicación clara para estos hallazgos. La variabilidad en los valores de la hormona podría verse afectada por el hecho de que no solamente es el estómago el encargado de secretar la ghrelina, sino que existen otros órganos que también inciden en su síntesis [9][10][11][12][13][14] , por lo que podríamos estar frente a un mecanismo de compensación. Por otra parte, si bien durante el acto quirúrgico se reseca gran parte del cuerpo y fondo gástrico, no hay seguridad de haber resecado toda el área donde se localizan las células liberadoras de la hormona.…”

“…La ghrelina es una hormona gástrica que actúa como regulador del apetito 8 . Se sintetiza principalmente en la mucosa del fondo y cuerpo gástrico, pero también es sintetizada en menor cantidad por el intestino delgado y aún en menor cuantía por el riñón, pulmón, placenta, testículos, ovarios, corazón, páncreas, hipófisis y placenta [9][10][11][12][13][14] . Niveles elevados de esta hormona estimulan la ingesta y su secreción comienza a disminuir a medida que la ingesta va aumentando 15 .…”