RESUMO
FSH and testosterone exert different regulatory effects on the seminiferous epithelium; they act through multiple and complex signaling routes to direct the development of the germ cells into mature spermatozoa. In addition to their well-known pathways of action, both hormones have recently been recognized to have new signaling routes that are linked to the Ca(2+) ion, including, among others, the regulation of cell proliferation by FSH and the regulation of cell migration by testosterone.
Assuntos
Hormônio Foliculoestimulante/fisiologia , Sistemas do Segundo Mensageiro/fisiologia , Células de Sertoli/metabolismo , Transdução de Sinais/fisiologia , Testosterona/fisiologia , Animais , Sinalização do Cálcio/fisiologia , Humanos , MasculinoRESUMO
The action of testosterone on the 45Ca2+ uptake and insulin secretion was studied in short-term experiments using isolated pancreatic islets of Langerhans. Testosterone (1 microM) stimulated 45Ca2+ uptake within 60 seconds of incubation on similar proportion than tolbutamide. Also, the hormone rapidly increased insulin release (34%; 180 seconds) on the presence of non-stimulatory concentrations of glucose (3 mM). Impermeant testosterone-BSA significantly stimulated the secretion of insulin to a lower percentage (10%). The action of the hormone is specific--neither 17beta-E2 nor progesterone stimulated insulin secretion in the presence of 3 mM glucose. The action of testosterone on insulin secretion was dose-dependent, and at rat plasma physiological concentrations (25 nM), stimulus was 17% (p < 0.05). In conclusion, in isolated pancreatic islets experiments, physiological concentration of testosterone rapidly stimulate insulin secretion and 45Ca2+ uptake through a membrane bound mechanism.
Assuntos
Insulina/metabolismo , Ilhotas Pancreáticas/efeitos dos fármacos , Testosterona/farmacologia , Animais , Cálcio/metabolismo , Relação Dose-Resposta a Droga , Secreção de Insulina , Ilhotas Pancreáticas/metabolismo , Masculino , Ratos , Ratos WistarRESUMO
In the present study, we investigated the mechanism by which isoproterenol hyperpolarises membrane potential (MP) in Sertoli cells from seminiferous tubules of 15-day-old rat testes. Modification of MP and resistance (R0) was analysed using conventional intracellular glass microelectrodes. Isoproterenol (2 x 10(-6) M) induced an immediate and significant hyperpolarisation in the Sertoli-cell membrane. The beta2-AR antagonist, butoxamine (1 x 10(-6) M), nullified isoproterenol action. The effect of the beta1 antagonist, metoprolol (1 x 10(-6) M), was light and non-significant. Sulphonylurea glibenclamide inhibition of the K+(ATP) channels suppressed isoproterenol action, and testosterone, while depolarising Sertoli-cell MP closing the K+(ATP) channels through the PLC/PIP2 pathway, reduced beta-AR agonist-induced hyperpolarisation. Also, polycations LaCl3 and spermine reversed isoproterenol's hyperpolarisation effect, probably depolarising the membrane potential through ionic interaction neutralising the action of isoproterenol on K+(ATP) channels. Adenylate cyclase agonist forskolin (0.1 microM) rapidly hyperpolarised Sertoli-cell MP, mimicking the isoproterenol effect. These effects indicate that isoproterenol's action on K+(ATP) channel probably involves the known signalling cascade beta-AR/Gs/AC/cAMP/PKA. These results suggest that the isoproterenol-induced hyperpolarisation is mediated by the opening of K+(ATP) channels in Sertoli cells. This beta-adrenergic hyperpolarisation might play a physiological role in the modulation of MP.
Assuntos
Transportadores de Cassetes de Ligação de ATP/agonistas , Agonistas Adrenérgicos beta/farmacologia , Isoproterenol/farmacologia , Canais de Potássio Corretores do Fluxo de Internalização/agonistas , Receptores Adrenérgicos beta 2/efeitos dos fármacos , Células de Sertoli/metabolismo , Animais , Colforsina/farmacologia , Relação Dose-Resposta a Droga , Eletrofisiologia , Glibureto/farmacologia , Hipoglicemiantes/farmacologia , Ativação do Canal Iônico/efeitos dos fármacos , Canais KATP , Lantânio/farmacologia , Masculino , Potenciais da Membrana/efeitos dos fármacos , Técnicas de Patch-Clamp , Ratos , Ratos Wistar , Células de Sertoli/efeitos dos fármacos , Testosterona/farmacologiaRESUMO
Testosterone at physiological intratesticular concentrations induces a dose-dependent depolarisation and an increase in input resistance together with an increment of 45Ca2+ uptake in the Sertoli cells from seminiferous tubules of immature rat. Previous studies have implicated K(+)ATP channels in these testosterone actions. This study demonstrates that testosterone and sulphonylureas (glibenclamide and tolbutamide) depolarise the membrane potential, augment resistance and 45Ca2+ uptake in the Sertoli cells of seminiferous tubules from 10-15 day-old rats. These actions were nullified by the presence of the K(+)ATP channel opener diazoxide. The depolarisation was also observed with the impermeant bovine serum albumin-bound testosterone. Testosterone actions were blocked by both pertussis toxin and the phospholipase C (PLC) inhibitor U73122 implying the involvement of PLC - phosphatidylinositol 4-5 bisphosphate (PIP2) hydrolysis via G protein in testosterone actions. Polycations, including spermine and LaCl3, depolarised the membrane potential and increased the resistance. Hyperpolarisation caused by EGTA was reversed by LaCl3 and by the presence of testosterone. This last effect was nullified by the presence of U73122. All of the above results indicate that the action of testosterone on the Sertoli cell membrane is exercised on the K(+)ATP channels through PLC-PIP2 hydrolysis that closes the channel, depolarises the membrane, and stimulates 45Ca2+ uptake.