Effects of luteinizing hormone and androgen on the development of rat progenitor Leydig cells in vitro and in vivo

Abstract

Progenitor Leydig cells are derived from stem cells. The proliferation and differentiation of progenitor Leydig cells significantly contributes to Leydig cell number during puberty. However, the regulation of these processes remains unclear. The objective of the present study was to determine whether luteinizing hormone (LH) or androgen contributes to the proliferation and differentiation of progenitor Leydig cells. Fourteen-day-old male Sprague-Dawley rats were treated for 7 days with NalGlu, which is a gonadotropinreleasing hormone antagonist, to reduce the secretion of LH in the pituitary and thus, androgen in the testis. Rats were co-administered with LH or 7a-methyl-nortestosterone (MENT), which is an androgen resistant to metabolism by 5a-reductase 1 in progenitor Leydig cells, and the subsequent effects of LH or androgen were measured.3 H-Thymidine was also intravenously injected into rats to study thymidine incorporation in progenitor Leydig cells. Progenitor Leydig cells were examined. NalGlu administration reduced progenitor Leydig cell proliferation by 83%. In addition, LH or MENT treatment restored Leydig cell proliferative capacity to 73% or 50% of control, respectively. The messenger RNA levels of proliferation-related genes were measured using real-time PCR. The expression levels of Igf1, Lifr, Pdgfra, Bcl2, Ccnd3 and Pcna were upregulated by MENT, and those of Pdgfra, Ccnd3 and Pcna were upregulated by LH. Both LH and MENT stimulated the differentiation of progenitor Leydig cells in vitro. We concluded that both LH and MENT were involved in regulating the development of progenitor Leydig cells.

Androgen and Luteinizing Hormone Stimulate the Function of Rat Immature Leydig Cells Through Different Transcription Signals

“…LH is essential for Leydig cell function because it is the principle stimulating hormone of androgen production in adult Leydig cells (1). Previous studies have shown that LH stimulated the development of rat progenitor Leydig cells into immature Leydig cells (5,11,20). In this study, we used 1 ng/ml LH instead of 100 ng/ ml because high concentration of LH can cause LHCGR internalization (28,29), and we also used a 2-day culture in which immature Leydig cells still maintained strong androgen production.…”

Intra-Testicular Signals Regulate Germ Cell Progression and Production of Qualitatively Mature Spermatozoa in Vertebrates

“…The testicular localization of GnIH and its receptor GPR147, in both mammals and birds, opens new perspectives in the autocrine/paracrine control of testicular activity suggesting a possible interplay between GnRH and GnIH in order to modulate T secretion and spermatogenesis ( 29 ). Furthermore, GnRH activity in Leydig cells is not restricted to T production but is extended to the development of rat progenitor Leydig cells both in vivo and in vitro ( 30 ).…”

Fetal programming of adult Leydig cell function by androgenic effects on stem/progenitor cells

“…Consequently, adult Leydig cells must develop from stem/progenitor cells (22,23). Numerous studies in rodents have investigated how adult Leydig cells differentiate from progenitor cells at puberty and have identified a number of factors involved (19,22,(24)(25)(26)(27)(28)(29). However, such studies focus around the period when stem/progenitor cells have started along the differentiation pathway into adult Leydig cells.…”