β2-adrenergic stimulation of androgen production by cultured mouse testicular interstitial cells

Abstract

The present studies characterized the β-receptor subtype involved in androgen production by cultured mouse testicular interstitial cells and explored the possible stimulation of androgen release by α-adrenergic agonists. During a 3-hour incubation period, LH and a non-specific β-adrenergic agonist, L-isoproterenol steadily increased androgen production with a similar time-course. Isoproterenol, epinephrine, norepinephrine and a specific β 2-receptor agonist, salbutamol stimulated androgen release in a concentration-dependent manner. The concentrations of the agonists required for half-maximum stimultion (EC 50 were approximately 1 nM (isoproterenol), 8 nM (epinephrine), 9 nM (salbutamol) and 2 μm (norepinephrine) giving an order of potency of isoproterenol > epinephrine = salbutamol ⪢ norepinephrine. L-but not the D-isomer of isoproterenol induced androgen production. A non-selective β-receptor antagonist, propranolol, abolished androgen production induced by isoproterenol. A selective β 2-receptor antagonist ICI 118, 551 inhibited the isoproterenol effect in a concentration-dependent manner with half-maximum inhibition (IC 50) at approximately 23 nM. The β 1-receptor antagonists, metoprolol and atenolol had no effect on isoproterenol-induced androgen release. The stimulatory effect of norepinephrine (an α-and β-agonist) was completely (100%) abolished by propranolol, unaffected by the α-antagonist phentolamine and only partially (35%) inhibited by phenoxybenxamine. Phenoxybenzamine and the α 2-agonist, clonidine reduced basal androgen production. These studies indicate that androgen production by primary cultures of mouse testicular interstitial cells occurs exclusively via the β 2-receptor subtype and that α-receptor agonists do not stimulate androgen release by these cells.