Endothelin-1 Stimulates Deoxyribonucleic Acid Synthesis and Contraction in Testicular Peritubular Myoid Cells1

Abstract

In the testis, endothelin-1 (ET-1) is produced by Sertoli cells, and it has been proposed to be a paracrine factor participating in the regulation of tubular and interstitial function. The response of purified testicular peritubular myoid cells (TPMC) to ET-1 was investigated in the present study. TPMC expressed a single class of high-affinity receptors that were shown by competitive binding experiments with sarafotoxin-6c to belong to the ETA subtype. The binding of ET-1 to TPMC was followed by rapid internalization of the receptor-ligand complex. ET-1 induced a prompt rise in intracellular Ca2+ concentration that was blunted in Ca(2+)-free medium and in the presence of Mn2+ or of voltage-operated-calcium-channel (VOC) blockers, indicating that both Ca2+ mobilization from intracellular stores and extracellular Ca2+ influx were involved. Thymidine uptake was promoted by ET-1 in a time-dependent manner, and the use of cyclo[D-Asp-L-Pro-D-Val-L-Leu-D-Trp] (BQ123) reduced the incorporation of thymidine. Protein kinase C (PKC) inhibition (100 nM calphostin C) abolished the ET-1 mitogenic effect. ET-1 also promoted TPMC contraction, as evaluated in collagen lattices, in a dose-related manner, with the half-maximal response observed at 1 nM. As in the case of mitogenesis, BQ123 blunted ET-1-induced contraction. PKC inhibition abolished ET-1-induced contraction. These findings indicate that ET-1 promotes DNA synthesis and contraction of TPMC and that both effects are mediated by PKC; they suggest as well that ET-1 may have a physiological role in the interaction between Sertoli cells and TPMC.

Identification and Characterization of Myosin from Rat Testicular Peritubular Myoid Cells1

“…Isolated STs were incubated with endothelin-1 for 20 second or 1 min with oxytocin [23]. SEM analysis of the STs showed that only endothelin-1 induced changes in PMC morphology, as previously demonstrated [24] (Fig.…”

Morphologic manifestations of testicular and epididymal toxicity

“…STF production is Contraction of PTMC is stimulated by endothelin-1 activity. 47,48 Although the precise mechanism for testicular degeneration associated with endothelin receptor antagonists has not yet been elucidated, it is plausible that altered fluid dynamics associated with PTMC impairment may contribute; vascular effects have also been considered. Necrosis of PTMC has been reported following administration of the histamine antagonist cimetidine to rats, with subsequent changes consistent with SC injury.…”

Exploring Human Testicular Peritubular Cells: Identification of Secretory Products and Regulation by Tumor Necrosis Factor-α

“…They can thus be viewed as structural cells bearing also the potential to contract (2,3). A major functional role of these smooth-muscle like cells (myoid cells) in the human species is assumed to be involvement in sperm transport (4).…”