Distinct Expression of Endothelin Receptor Subtypes A and B in Luteinized Human Granulosa Cells

Abstract

Endothelins (ET) are potent vasoconstrictive peptides originally isolated from vascular endothelial cells. Their biological effects are mediated through two different receptors, the endothelin-1 (ET-1)-selective endothelin receptor subtype ETA and the non-selective receptor subtype ETB. ET-1 protein has been found in human ovarian follicular fluid and ET-1 mRNA expression has been demonstrated in ovarian tissue. These findings indicate that the endothelin-system participates in the modulation of ovarian function, probably acting in an autocrine/paracrine manner. In the current study we used freshly aspirated, luteinized human granulosa cells (hGC) representing an in vitro model of the early corpus luteum. By means of RT-PCR and immunocytochemistry we investigated whether luteinized human granulosa cells express ETA and ETB receptors. Specific amplification products of ETA transcripts were detected in all samples investigated. In contrast, only after using a three-fold amount of ETB reverse transcripts we were able to demonstrate specific, but weak amplification products. In addition, immunocytochemical staining for ETA but not for ETB was found in granulosa cell preparations. The present study provides clear evidence that human granulosa cells predominantly express ETA receptor subtype mRNA and protein hinting to its possible role in follicle maturation and corpus luteum formation.

Altered endothelin expression in granulosa-lutein cells of women with polycystic ovary syndrome

“…In the current study, we compared the expression profile of the endothelin system and its effect on GLC functions in women with the polycystic ovary syndrome and age-matched normally ovulating women undergoing follicular aspiration during an IVF cycle. Our findings also support previous reports showing that endothelins are present in follicular fluid (Gentili et al, 2001;Haq et al, 1996). Their levels in the follicular fluid are significantly higher than their levels in the serum (Choi et al, 2011), suggesting that endothelins are produced endogenously.…”

The level of vascular endothelial cell growth factor, nitric oxide, and endothelin-1 was correlated with ovarian volume or antral follicle counts: A potential predictor of pregnancy outcome in IVF

“…ET-1 is a potent and longacting vasoconstrictive peptide. Its receptor, endothelin, plays a role in the formation of the human corpus luteum and the maturation of follicles (Gentili et al 2001). Our data showed a reduction in ET-1 concentration in the women who became pregnant following IVF.…”

Why two endothelins and two receptors for ovulation and luteal regulation?

“…The theca interna is a highly vascularized cell layer that contains steroidogenic cells and separates the theca externa from the core of the follicle. The endothelin receptor expression is also apparent in the granulosa cells of the follicle (Gentili et al, 2001) as well as the corpus luteum. In the corpus luteum, the ET A receptor is expressed in the small and large luteal cells (Mamluk et al, 1999), and both receptor subtypes are localized in the endothelial cells of this highly vascularized tissue (Karam et al, 1999;Mamluk et al, 1999).…”