Diurnal Rhythmicity of Beta-1- and Beta-2-Adrenergic Receptors in Ovariectomized, Ovariectomized Estradiol-Treated and Proestrous Rats

Abstract

The effect of norepinephrine on LH is complex: the ovarian steroidal milieu appears to determine whether norepinephrine stimulates or inhibits LH secretion. It has been proposed that steroids allow norepinephrine to have opposite effects on LH by altering the relative concentrations of α₁-(stimulatory) and β-(inhibitory) adrenergic receptors in the hypothalamus. Thus, many investigators have argued that estradiol may permit norepinephrine to stimulate LH release by increasing the density of α₁- and decreasing the density of β-adrenergic receptors in one or more key hypothalamic regions. To test this hypothesis specifically, we measured the density of β₁- and β₂-adrenergic receptor densities in proestrous, ovariectomized, and ovariectomized estradiol-treated rats at various times of day to determine (1) whether the densities of β-receptors exhibit diurnal rhythmicity, (2) whether β-receptors decrease during the time of increased LH secretion and/or (3) how steroidal milieu influences the density and/or the rhythm of receptor densities. The densities of β₁- and β₂-receptors exhibit a diurnal rhythm in some brain areas. These rhythms are detectable only in proestrous and ovariectomized rats and only in selected brain regions. Estrogen treatment has opposing effects in different brain regions. It suppresses the rhythm of β₁-receptor concentrations in ovariectomized rats and also suppresses the average density of receptors in the suprachiasmatic nucleus and pineal gland. In contrast, estrogen increases the density of β₁-receptors in the medial preoptic nucleus. In summary, the results of this study demonstrate that the diurnal rhythm in β-receptors and the effect of estradiol correlate with previously reported changes in receptor-mediated functions. In addition, they reveal the complex interactions of time of day and steroidal milieu on the density of β₁- and β₂-receptors in various brain regions. Finally, the data strongly suggest that decreases in the densities of β-receptors cannot explain the timing of the proestrous or estradiol-induced LH surge or the ability of norepinephrine to inhibit LH release in ovariectomized rats or stimulate LH release in steroid-treated rats.

Effects of Sex Hormones on the Pineal Response to Isoproterenol and on Pineal Beta-Adrenergic Receptors

“…This is in good agreement with the study of Weiland and Wise [14]. On the other hand, Vacas and Cardinali [12] showed no effect of oestradiol on pineal P-adrenergic receptor density probably because they (1) The stimulating effect of testosterone on pineal Padrenergic receptors in male rats in the present study is contrary to another study conducted by Vacas et al [13], in which testosterone depressed the pineal P-adrenergic receptor content in castrated rats.…”

“…The time of injection of ISO was chosen to eliminate the influence of dark. Rhythms in the density of pineal p-adrenergic receptors have been previously reported in which a peak value occurs just prior to lights off [16] or in the middle of the dark phase [14,17] Collection o f Serum and Pineal Gland. After 5 days of treatment with EB, TP or vehicle, animals were injected i.p.…”

“…During pro-oestrous or after oestradiol administration in ovariectomized rats, there is a reduction in the pineal adenylate cyclase response [ 10] and in levels of cAMP induced by norepi-nephrine [11]. More recently, Alonso and coworkers re ported that pineal melatonin responses to isoproterenol (ISO) changed as a function of the stage of the rat oestrous cycle [2], that oestradiol blocked the ISO-induced eleva tion of pineal melatonin in ovariectomized rats [2] and that castration abolished the nocturnal rise of both tyro sine hydroxylase and pineal melatonin in male rats [6], Effects of sex hormones on pineal P-adrenergic receptors in rats have also been reported although the results are inconsistent [12][13][14]. Thus, it is possible that sex hor mones may regulate pineal melatonin production through modification of the pineal P-adrenergic system.…”

Estrogen modulation of adrenoceptor responsiveness in the female rat pineal gland: differential expression of intracellular estrogen receptors

“…In addition to this modulation in the efficiency of the intracellular transduction pathway, a complementary action mechanism for estrogen could involve the regulation of density and/or affinity of β ‐adrenergic receptors. As this respect, a decrease in the number of β ‐adrenergic receptors in the pineal gland of ovariectomized rats treated with E 2 has been previously observed [31], an effect which is reflected in a decrease in the rate of melatonin production in response to the administration of ISO in vivo [9]. In our case, we have been unable to observe significant differences in the amount of mRNA encoding the β ‐adrenoceptor by RT‐PCR (data not shown).…”

Circadian Rhythms during Aging

“…Circadian rhythms of serotonin and norepinephrine levels and turnover, and 1 -, 1 -and 2 -adrenergic receptor density have all been reported to be altered in the brains of aging female rats [53][54][55][56].…”