Adrenomedullin Inhibits the Contraction of Cultured Rat Testicular Peritubular Myoid Cells Induced by Endothelin-11

Abstract

The present study documents that adrenomedullin (AM), a vasoactive peptide originally identified in pheochromocytoma tissue and present in the testis, in vitro affects the function of testicular peritubular myoid cells (TPMC), a contractile cell type located in the seminiferous tubule wall. AM stimulated cAMP production by cultured TPMC taken from 16-day-old rats, and this effect was completely inhibited by the AM antagonist AM-(22-52) and partially by the CGRP (calcitonin gene-related peptide) antagonist CGRP-(8-37). Studies on TPMC contractile activity documented that AM inhibits TPMC contraction induced by endothelin-1 (ET-1) and that its effect is antagonized by AM-(22-52). Neutralizing AM produced by TPMC with the addition of anti-AM antibody induced a significant increase of ET-1-induced contraction. When exposed to the protein kinase A inhibitor H-89, AM inhibitory activity on ET-1-induced TPMC contraction was suppressed, whereas the nitric oxide synthase inhibitor N:(G)-nitro-L-arginine methyl esther did not modify AM activity. In conclusion, our study indicates that AM stimulates cAMP production and inhibits the contraction induced by ET-1 in TPMC in vitro, and that AM produced by TPMC has an autocrine effect. We propose that AM may have a role in the control of seminiferous tubule contraction.

Adrenomedullin Peptide: Gene Expression of Adrenomedullin, its Receptors and Receptor Activity Modifying Proteins, and Receptor Binding in Rat Testis—Actions on Testosterone Secretion1

“…The discrepancy of the cell types expressing ADM may be due to species differences. ADM may be one of the local factors controlling the contraction of seminiferous tubules as ADM is able to antagonize EDN1-induced contraction of testicular peritubular myoid cells [19]. In the present study, we found that ADM may regulate steroidogenesis as ADM significantly reduced hCG-stimulated testosterone release by acting on its specific receptors, an inhibitory effect that was abolished by ADM .…”

“…Recent studies have also shown the gene expression or peptide of Adm in reproductive organs such as the ovary [13,14], uterus [13,15], testis [12], prostate [16,17], and epididymis [18]. In addition, ADM inhibits endothelin 1 (EDN1)-induced contraction of seminiferous tubules [19], in which ADM receptors are found in testicular peritubular myoid cells [20]. These findings suggest that ADM may play a role in the male reproductive system.…”

Adrenomedullin increases ciliary beat frequency and decreases muscular contraction in the rat oviduct

“…This effect was mostly mediated by the ADM receptor. These opposite effects of ADM and endothelin (ET) on muscle contraction have already been reported in the vasculature (Stangl et al 2001) and in the testis (Santiemma et al 2001). Endothelin was a 21 amino acid vasocontricting peptides produced primarily in the endothelium and plays a key role in vascular homeostasis.…”

Oligozoospermia with normal fertility in male mice lacking the androgen receptor in testis peritubular myoid cells

“…Our in vivo studies show that PM-AR Ϫ/y mice might have some defects in contractility, thus resulting in decreased sperm output. Earlier studies demonstrated that ET-1 and AM are two balancing factors that control PM cell contraction (35)(36)(37)(38)(39). It is possible that androgen͞AR may go through the modulation of ET-1 and AM (Fig.…”