Leydig cells secrete factors which increase vascular permeability and endothelial cell proliferation

Abstract

Adult intact control rats, and animals treated with human chorionic gonadotrophin (hCG) or with ethane dimethane sulphonate (EDS) to deplete Leydig cells, were injected with bromodeoxyuridine (BrdU) to label proliferating cells. Apoptotic cells were visualized by in-situ end labelling (ISEL) of fragmented DNA. Three per cent of testicular endothelial cells were labelled with BrdU and few were apoptotic in intact testes. The BrdU endothelial cell labelling index was increased by hCG-treatment and decreased in Leydig cell-depleted testes. Immunohistochemical staining showed that Leydig cells and testicular macrophages contain immunoreactive vascular endothelial growth factor (irVEGF). The ability of testicular cells to stimulate angiogenesis was studied further by transplanting interstitial cells or seminiferous tubule segments under the kidney capsule. A prominent vascular network was observed around interstitial cell grafts, but not around tubule grafts. Treatment of transplanted rats with human chorionic gonadotrophin (hCG, 50 i.u.) resulted in an accumulation of PMN-leukocytes and an increase in vascular permeability in the remaining testis and in interstitial cell grafts. Interstitial cells from Leydig cell-depleted (EDS-treated) testes were also transplanted under the kidney capsule. This type of graft caused only a discrete stimulation of angiogenesis, and there was no increase in vascular permeability around the graft after hCG treatment. It is suggested that Leydig cells secrete angiogenic factors and that they are the source of the inflammation mediator(s) produced in the testis after hCG treatment. The high proliferation rate in endothelial cells suggests continuous remodelling of the testicular microvasculature, but the functional significance of this remains unknown.

The endocrine-gland-derived VEGF homologue Bv8 promotes angiogenesis in the testis: Localization of Bv8 receptors to endothelial cells

“…Angiogenesis is also essential in adult physiology for wound healing and, prominently, for reproductive functions (2). Although angiogenesis is most commonly associated with the cyclical proliferative events in the female reproductive tract, most species also display a surprisingly high rate of endothelial cell turnover within the testis (3).…”

Testicular angiogenic activity in response to food restriction in rabbits

“…Besides, androgen receptors have been shown in endothelial cells in rat and human prostate (El Alfy et al 1999, Pelletier et al 2000. The high proliferation rate in endothelial cells suggests remodeling of the testicular microvasculature (Collin & Bergh 1996), which might have occurred in the testes of the most food-restricted rabbits (group C), in the present study. Since, in the hamster, increased angiogenesis and rapid renewal of testicular microvasculature is fundamental for physiologic seasonal testicular recrudescence (Mayerhofer et al 1989), a raise in angiogenesis in the rabbit testes during puberty may be a compensatory mechanism to overcome nutritional impairment.…”

“…It has been suggested that Leydig cells secrete angiogenic factors (Collin & Bergh 1996). A study on adult mice supported the concept that VEGFA stabilizes mature vessels in adult tissues, such as the testes (Maharaj et al 2006).…”

“…However, endothelial cell proliferation was higher in male reproductive organs, such as the testes, than in liver, muscle, and brain (Lissbrant et al 2003). A continuous turnover of endothelial cells, accompanied by apoptosis of these cells, has been reported in male reproductive organs under normal conditions (Collin & Bergh 1996). In the prostate, blood vessel endothelial cells are stimulated by locally synthesized androgens to produce paracrine growth factors that can promote the growth of secretory epithelium (Franck-Lissbrant et al 1998).…”

The gonadotropins: Tissue-specific angiogenic factors?

“…The unfenestrated endothelial cells of the testis showed at least 10-fold higher proliferation rate when compared to most other organs (Collin and Bergh, 1996). This rate could be further increased by hCG stimulation of Leydig cells (Collin and Bergh, 1996).…”