Direct Effect of Estradiol on the Number of Dopamine Receptors in the Anterior Pituitary of Ovariectomized Rats

Abstract

The effect of 17 beta-estradiol (17 beta E2) on anterior pituitary dopaminergic receptor (D2) content was studied in vitro in relation to PRL secretion. Anterior pituitaries from ovariectomized rats were incubated for short periods in medium 199, with or without the steroid. Dopamine (DA) receptors in partially purified pituitary membranes were quantified by equilibrium binding using [3H]spiperone; the PRL released into the incubation medium was analyzed by RIA. Addition of 10(-10) to 10(-6) M 17 beta E2 to the incubation medium of anterior pituitaries rapidly and reversibly decreased the number of DA receptors (P less than 0.01 to 0.001), while increasing PRL release, in a dose-related fashion. The maximal effect on both receptor numbers and PRL secretion was obtained with 10(-8) M 17 beta E2. This effect involved no change in receptor affinity (Kd = 0.11 +/- 0.01 nM in presence or in absence of 17 beta E2). This estrogen-induced decrease in DA-binding capacity was apparently not the result of the occupation of spiperone binding sites by the steroid, since after a 30-min incubation with 10(-8) M [3H]17 beta E2, no radioactivity was detectable on the partially purified membranes. Moreover, the presence of 17 beta E2 at the same time as the labeled D2 ligand did not modify the kinetics of association or dissociation of spiperone with pituitary membranes. This decrease in anterior pituitary DA receptor content and the increase in PRL release were already significant after a 7-min incubation in the presence of 10(-8) M 17 beta E2. Finally, these effects of 17 beta E2 were not mimicked by its 17 alpha-stereoisomer, nor by progesterone, or testosterone. These results suggest that the stimulatory effect of 17 beta E2 on PRL secretion may be due, at least in part, to the desensitization of anterior pituitary cells to DA. The steroid may produce this desensitization directly by decreasing the number of D2. The short latency of this effect likely discards the possibility of a genomic action of 17 beta E2.

Effects of estradiol and progesterone on prolactin transcriptional activity in somatolactotrophic cells

“…Although it is well known that dopamine plays a major role in the control of prolactin release [4,11], prolactin synthesis and secretion are also regulated by several hypothalamic hormones. Thyrotropin-releasing hormone (TRH) is a primary secretagogue [12].…”

“…It has been reported that there is marked hyperplasia of lactotrophs during pregnancy and lactation in humans [2]. Exogenous E2 is known to induce lactotroph hyperplasia [3], and increases prolactin release from rat pituitary cultures by desensitizating lactotrophs to dopamine, a well-known inhibitor of prolactin release [4]. E2 was also reported Effects of estradiol and progesterone on prolactin transcriptional activity in somatolactotrophic cells Tselmeg Mijiddorj, Haruhiko Kanasaki, Indri Purwana, Sukhbaatar Unurjargal, Aki Oride and Kohji Miyazaki…”

“…Ligand-bound ERs form dimers that act on specific estrogen response elements in the promoter regions of estrogen-regulated genes. Three major ER isoforms are known to be expressed in the rat anterior pituitary: ERα, ERβ, and truncated estrogen receptor product-1 (TERP-1) [7], and each isoform is regulated throughout the estrous cycle and by steroids and hypothalamic peptides [8][9][10].Although it is well known that dopamine plays a major role in the control of prolactin release [4,11], prolactin synthesis and secretion are also regulated by several hypothalamic hormones. Thyrotropin-releasing hormone (TRH) is a primary secretagogue [12].…”

Absence of direct regulation of prolactin cells by estradiol-17β in rainbow trout (Oncorhynchus mykiss)

“…17&Estradiol (E,) stimulates PRL secretion by a direct action on pituitary cells in which it both enhances PRL mRNA production dramatically and increases the mitotic activity of PRL cells (Lieberman et al, 1982;Takahashi and Kawashima, 1987). Moreover, in vitro studies suggest that the direct effect of E, on PRL cells could be exerted by two other mechanisms: an increase in their sensitivity to thyrotropin-releasing hormone (TRH), one of the most potent PRL-releasing factors (PRF), and a decrease in their sensitivity to dopamine, considered as the most likely PRL-inhibiting factor (De Lean et al, 1977;Pasqualini et al, 1986;Zhang et al, 1990). Further in vivo studies also indicate that estrogens not only act directly on the lactotrophs but also modulate activity of the central system which controls PRL pituitary release (Fink, 1988).…”

Effect of 17 β-Estradiol on Phosphoinositide Metabolism and Prolactin Secretion in Anterior Pituitary Cells

“…In addition, estrogens exert demonstrable effects on rat PRL synthesis and gene transcrip tion [4,7]. Pasqualini et al [8] reported that 17 |)-estradiol (E2) had a direct effect on the number of dopamine receptors in the anterior pituitary of ovariectomized rats, and suggested that the stimulatory effect of estradiol on PRL secretion may be due to the desensitization of these cells to dopamine. The effect estra diol exerts on PRL release can be shown using long-term cultures of dispersed anterior pituitary cells with a suitable Received: October 3, 1988 Accepted after revision : February 23, 1989 preincubation time, but it is rare to duplicate this effect using short-term cultures.…”