Ovarian β-Adrenergic Receptors during the Onset of Puberty: Characterization, Distribution, and Coupling to Steroidogenic Responses*

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Abstract
In an attempt to study the involvement of an adrenergic mechanism in the control of ovarian function at puberty, the presence of β-adrenergic receptors wets demonstrated, and the receptors were characterized in pre- and peripubertal ovaries. Using [125I]iodohydroxybenzylpindolol (IHBP) as a ligand, a single class of high affinity, low capacity β-adrenergic sites was found in both granulosa cells and residual ovary. Analysis of Scatchard plots derived from saturation curves or kinetic analysis of association curves provided identical equilibrium dissociation constant (Kd) values for the ligand-receptor binding. Dissociation experiments showed that the ligand binding to the receptor had the presence of both loosely bound, easily displaceable and tight, nondisplaceable components. IHBP binding was inhibited by L-propranolol [inhibition constant (Ki) = 10.5 nM], isoproterenol (Ki = 696 nM), and zinterol, a β2-adrenergic agonist (Ki = 187 nM). Metoprolol, a β1-antagonist, exhibited a much higher Ki (5.3 μM). Computer analysis of the binding parameters indicated that more than 99% of the binding sites were β2- Receptor content in both granulosa cells and residual ovary increased significantly between the anestrous and the late proestrous phases of puberty. The receptor content of whole ovaries increased significantly between anestrus and the morning of late proestrus, decreased at the time of the first LH surge, remained low during estrus, and increased strikingly on the day of first diestrus. In all pubertal stages, receptor affinity appeared to be essentially the same (Kd for IHBP = 0.1–0.2 nM). Incubation of peripubertal ovaries with zinterol, a β2-adrenergic agonist, induced progesterone release from early proestrous and late proestrous ovaries, but not from anestrous ovaries. A marked increase in progesterone response was observed after ovulation, i.e. in estrous and diestrous day 1 animals. Zinterol induced androstenedione release at all pubertal phases, but elicited testosterone release only from early proestrous and late proestrous ovaries. The agonist failed to produce a significant increase in estradiol release at any phase of puberty studied. The results indicate that the immature ovary contains a population of β- adrenergic sites of the β2-type, and that stimulation of these receptors elicits steroid release, in a differential manner, during the days encompassing the first ovulation. The findings that a steroidogenic response to β2-adrenergic stimulation develops during the early proestrous phase of puberty and that both the β-receptor content and the progesterone response increase after the first ovulation suggest the involvement of an adrenergic mechanism in the initiation of adult ovarian function.