Estradiol and its membrane-impermeable conjugate estradiol-BSA inhibit tamoxifen-stimulated prolactin secretion in incubated rat pituitaries.
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(-8) M estradiol-17beta (E2) 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 E2, and the effect of different ER ligands (ICI182780, TX, estradiol-17alpha, E2 -BSA) on TX-stimulated PRL secretion. Moreover, the effect of E2 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 E2 supressed the PRL releasing effect of injected TX; ii) whereas coincubation with the pure anti-E type II ICI182780 antagonized the inhibitory effect of E2, coincubation with the anti-E type I TX did not; iii) estradiol-17alpha lacked inhibitory action, whereas a dose-dependent inhibitory effect of both E2 and E2 -BSA was noticed; and iv) TRH stimulatory effect on PRL release in pituitaries from TX-treated rats was blocked by addition of E2 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 E2 inhibition of TX-stimulated PRL secretion.
Aguilar
R
R
Department of Cellular Biology, Physiology and Immunology, University of Córdoba Avda, Menendez Pidal s/n, 14004 Córdoba, Spain.
Bellido
C
C
Garrido-Gracia
J C
JC
Alonso
R
R
Sánchez-Criado
J E
JE
D000818:Animals; D003864:Depression, Chemical; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D012710:Serum Albumin, Bovine / Q000494:pharmacology*; D013629:Tamoxifen / Q000494:pharmacology*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology
D004965:Estrogen Antagonists; D020845:Selective Estrogen Receptor Modulators; C043090:estradiol-bovine serum albumin; D013629:Tamoxifen; C074283:estradiol 3-benzoate; D000077267:Fulvestrant; D012710:Serum Albumin, Bovine; D004958:Estradiol; D013973:Thyrotropin-Releasing Hormone; D011388:Prolactin