Estradiol and its membrane-impermeable conjugate estradiol–BSA inhibit tamoxifen-stimulated prolactin secretion in incubated rat pituitaries

Abstract

In the absence of estrogen (E), the selective E receptor modulator tamoxifen (TX) has two agonist effects in the rat pituitary: induction of progesterone receptor (PR)-dependent GnRH self-priming in the gonadotrope, and stimulation of prolactin (PRL) secretion in the lactotrope. TX-induced gonadotropin (GnRH) self-priming is absent when 10 28 M estradiol-17b (E 2 ) is added to the incubation medium of pituitaries from TX-treated rats. The present experiments investigated whether PR-independent PRL release into the incubation medium of pituitaries from TX-treated ovariectomized (OVX) rats was affected by E 2 , and the effect of different ER ligands (ICI182780, TX, estradiol-17a, E 2 -BSA) on TX-stimulated PRL secretion. Moreover, the effect of E 2 on TRH-stimulated PRL secretion in pituitaries collected from estradiol benzoate-and TX-treated OVX rats was studied. It was found that: i) incubation with E 2 supressed the PRL releasing effect of injected TX; ii) whereas coincubation with the pure anti-E type II ICI182780 antagonized the inhibitory effect of E 2 , coincubation with the anti-E type I TX did not; iii) estradiol17a lacked inhibitory action, whereas a dose-dependent inhibitory effect of both E 2 and E 2 -BSA was noticed; and iv) TRH stimulatory effect on PRL release in pituitaries from TX-treated rats was blocked by addition of E 2 to the medium. Taken together, these data argue in favor of the presence of specific membrane recognition sites for E in the lactotrope involved in steroid-specific E 2 inhibition of TX-stimulated PRL secretion.

17β-Estradiol stimulates the translocation of endogenous estrogen receptor α at the plasma membrane of normal anterior pituitary cells

“…In pituitary tumoral GH3/B6/F10 cells, ERa was visualized by immunofluorescence, suggesting its association with the plasma membrane (Norfleet et al, 1999(Norfleet et al, , 2000. In addition, the presence of the membrane ER has been indirectly suggested by rapid activation of different signaling pathways (Aguilar et al, 2006;Bulayeva et al, 2004Bulayeva et al, , 2005. However, there is no good evidence that ERa spans the membrane or contains an extracellular domain.…”

Oestrogen Signalling and Neuroprotection in Cerebral Ischaemia

“…However, because the above studies principally used E 2 , which can activate both extranuclear and nuclear oestrogen receptors, it has been difficult to distinguish the importance and contribution of extranuclear receptor‐mediated signalling in E 2 neuroprotective effects. To address this issue, we employed two E 2 conjugates, E 2 ‐bovine serum albumin (BSA) conjugate (100–102) and the newer E 2 dendrimer conjugate (EDC) (103), which, as a result of their size and charge, cannot enter the cell nucleus. EDC and E 2 ‐BSA retain their ability to induce rapid extranuclear‐mediated nongenomic signalling, but lack significant nuclear ER‐mediated genomic signalling ability as a result of their inability to enter the cell nucleus and interact with nuclear ER (102,103).…”

Extranuclear Estrogen Receptors Mediate the Neuroprotective Effects of Estrogen in the Rat Hippocampus

“…To address this issue, the current study employed two E2 conjugates, E2-BSA conjugate [30], [31], [32] and the newer E2 dendrimer conjugate (EDC) [33], which due to their size and charge cannot enter the cell nucleus. EDC and E2-BSA retain their ability to induce rapid extranuclear-mediated nongenomic signaling, but lack significant nuclear ER-mediated genomic signaling ability due to their inability to enter the cell nucleus and interact with nuclear ER [32], [33].…”