PARENT SESSION
PITUITARY AND GONADOTROPINS

Tuesday, August 3, 2004
10:30 AM–12:30 PM
Buchanan Courtyard

(365) GONADOTROPE ESTROGEN RECEPTOR AND AND PROGESTERONE RECEPTOR IMMUNOREACTIVITY AFTER OVARIECTOMY AND EXPOSURE TO ESTRADIOL BENZOATE, TAMOXIFEN OR RALOXIFENE: CORRELATION WITH LH SECRETION.

Sanchez-Criado, Jose E.¹, Martin de las Mulas, Juana², Bellido, Carmen¹, Aguilar, Rafaela¹, Garrido-Gracia, Jose Carlos¹, ¹ Dpt. Cell Biology, Physiology and Immunology, Cordoba, Spain² Dpt. Comparative Pathology, Cordoba, Spain

ABSTRACT- The SERM tamoxifen (TX) has agonist/antagonist actions on LH secretion in the rat. Whereas in the absence of E, elicites progesterone receptor (PR)-dependent GnRH self-priming, TX antagonizes E stimulatory action on LH secretion. The aim of these experiments was to explore whether TX treatment-induced differential expression of ER and ER in the gonadotrope may determine its agonist effect on LH secretion. In the first experiment, basal, GnRH-stimulated LH secretion and GnRH self-priming were studied in incubated pituitaries from intact rats in metestrus or proestrus, or from two weeks OVX-rats injected over three days with 0.2 ml oil, 25 g estradiol benzoate (EB), 3 mg TX or 1 mg raloxifene (RX) and incubated further with medium alone, estradiol17 (E2), TX or RX, respectively. GnRH was added to the incubation medium for 15 min 1 hour appart. In addition, we tested the effect of the blokade of activation of PR by adding ZK299 in the incubation medium. In the second experiment, pituitaries from all six groups were immunostained for PR and for co-localization of ER and ER in the gonadotrope. In the E environment pituitaries exhibited a robust response to GnRH and a PR-dependent GnRH self-priming.TX, but not RX, without affecting GnRH-stimulated LH secretion, induced a PR-dependent GnRH self-priming. Whereas OVX reduced nuclear PR-IR to undetectable levels, EB and TX increased the number of LH cells expressing nuclear PR and reduced OVX-cells. RX had not effect on these parameters. Based on these findings, and on the existence in the pituitary of two ER subtypes we tested the hypothesis that the proportion of ER or in the gonadotrope may differ under the effect of the different ligands. We found that either EB or TX, but not RX, decreased the number of OVX-cells. Also, we found a higher percentage of LH-positive cells expressing ER-IR in pituitaries from proestrous rats and from OVX-rats treated with TX, while a lower percentage of LH-positive cells for ER was found in RX-treated rats. No differences were noticed in LH cells expressing ER-IR. Thus, the TX-induced PR-dependent GnRH self-priming was positively correlated with the number of both gonadotropes and LH-IR positive cells expressing ER suggesting that TX, like the cognate ligand, may regulate the secretion of LH through ER subtype containing active gonadotropes.

KEY WORDS: estrogen receptors, selective estrogen receptor modulators, progesterone receptor, GnRH self-priming