The action of calcitonin on the TM4 Sertoli cell line and on rat Sertoli cell-enriched cultures.
The effects of synthetic salmon calcitonin on primary Sertoli cell-enriched cultures and on an established cell line (TM4 cells, derived from immature mouse Sertoli cells) were studied. Synthetic salmon calcitonin stimulated the conversion of [3H]adenine to [3H]cyclic AMP in both cell systems. In addition, this peptide stimulated the secretion of rABP in primary Sertoli cell-enriched cultures prepared from rat testis. Calcitonin also increased the total concentration of both androgen and estrogen receptors in TM4 cells. Because cAMP analogs decreased androgen and estrogen receptor concentrations, the effect of calcitonin on sex steroid receptors may not be mediated by its effect on cyclic AMP in these cells. The possibility that the action of synthetic salmon calcitonin on the receptors might be mediated by a change in cellular Ca2+ was investigated. Lowering extracellular Ca2+ concentrations from 1.5 mM to less than 0.01 mM markedly reduced the concentration of androgen and estrogen receptors; restoration of Ca2+ to 1.5 mM returned receptor levels to normal. When the receptor concentrations were decreased by lowering extracellular Ca2+ concentrations to 0.5 mM, treatment with the calcium ionophore, A23187, restored receptor levels to normal. Although the calcium channel blocker, verapamil, decreased receptor levels, calcitonin partially counteracted its effect. Trifluoperazine, an inhibitor of calmodulin, also diminished androgen and estrogen receptor, levels in the cytosol of TM4 cells. It was concluded that calcitonin stimulates the formation of cyclic AMP and the secretion of rABP by Sertoli cells. This peptide also increases the concentration of androgen and estrogen receptors, possibly by a mechanism that is, in part, Ca2+ -mediated. These results, along with those on Leydig cells, suggest that calcitonin could be a regulator of testicular function.
Nakhla
A M
AM
Population Council, New York, New York 10021.
Mather
J P
JP
Jäne
O A
OA
Bardin
C W
CW
D000727:Androgen-Binding Protein / Q000378:metabolism; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002116:Calcitonin / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002467:Cell Nucleus / Q000032:analysis / Q000648:ultrastructure; D000242:Cyclic AMP / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D051379:Mice; D051381:Rats; D011919:Rats, Inbred Strains; D011944:Receptors, Androgen / Q000032:analysis / Q000187:drug effects; D011960:Receptors, Estrogen / Q000032:analysis / Q000187:drug effects; D012708:Sertoli Cells / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D014268:Trifluoperazine / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D000727:Androgen-Binding Protein; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D014268:Trifluoperazine; D000001:Calcimycin; D002116:Calcitonin; D014700:Verapamil; D000242:Cyclic AMP; D002118:Calcium