Growth of the male external genitalia is primarily regulated by androgens; however, several observations suggest growth hormone (GH) or a GH dependent factor, such as insulin-like growth factor-1 (IGF-1), might also be involved. It is hypothesized that testosterone (T) might induce the synthesis of IGF-1 or IGF-binding protein (IGF-BP) which could affect cell proliferation. This was evaluated by determining the effect of T on thymidine incorporation, cell surface IGF-1 binding, and the production of IGF-1 and IGF-BP by cultured neonatal foreskin fibroblasts. Testosterone significantly increased thymidine incorporation and the production of IGF-1 and IGF-BP (p < 0.05 vs control). However, T significantly decreased the cell surface binding of IGF-1 (p < 0.0001 vs control). To determine whether or not the increase in IGF-1 production was important in mediating the effect of T on thymidine incorporation, cells were incubated with either anti-IGF-1 antibody (anti-IGF-1), anti-IGF-1-receptor antibody (IGF-1-R-Ab), or a non-specific control antibody (NS-Ab). Anti-IGF-1 significantly decreased thymidine incorporation in both control cultures and those containing T. In addition, IGF-1-R-Ab blocked the expected T dependent increase in thymidine incorporation, while NS-Ab had no effect. These in vitro observations suggest both T and IGF-1 affect neonatal foreskin fibroblasts in a complex relationship. In addition, these data suggest T might stimulate foreskin fibroblast proliferation, at least in part, by changing the balance in production and effects of IGF-1 and IGF-BP.

Cells, Cultured↗

PubMedDate not supplied

[Clinical evaluation of abutment teeth and mucosal membrane below the bridge in patients after removal of prosthetic bridges].

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Dental Abutments↗

PubMedDate not supplied

Sphingomyelinase inhibits in vitro Leydig cell function.

Activation of the immune system has profound effects on endocrine function which are mediated by cytokines including tumor necrosis factor-alpha (TNF alpha). In vitro, TNF alpha has been shown to directly inhibit Leydig cell testosterone (T) production, but the mechanism of this effect is still unclear. Recent studies using cultured human fibroblasts have shown that TNF alpha stimulates the activity of neutral sphingomyelinase (SMase) which hydrolyses sphingomyelin (SM) generating ceramide and changing membrane components including cholesterol. The cellular affects of increased SMase activity have been reproduced in vitro by the addition of exogenous SMase. In cultured fibroblasts, exogenous SMase decreases cholesterol synthesis. These findings led us to hypothesize that SMase might be important in the regulation of steroid hormone synthesis. To our knowledge, no previous studies have investigated this possibility. To test this hypothesis, rat Leydig cell enriched cultures were incubated in media containing SMase (0.1 to 100 mU/ml) or in control media. SMase significantly decreased basal and human chorionic gonadotropin (hCG) stimulated T production. SMase also decreased hCG binding and hCG stimulated adenosine 3':5'-cyclic monophosphate (cAMP). N-acetyl-sphingosine (0.1 to 10 microM), a water soluble ceramide, was used to determine whether or not the effects of SMase could be reproduced by ceramide addition. N-acetyl-sphingosine had only slight effects on basal T and cAMP, and no effect on hCG binding or hCG stimulated T or cAMP. These data suggest the metabolism of membrane sphingomyelin may be an important regulatory pathway in the control of Leydig cell function.

Animals↗