Effects of Estrogens on the Ultrastructural Characteristics of Female Rat Prolactin Cells as Evaluated by in situ Hybridization in Combination with Immunogold Staining Technique

El‐Alfy²,

Labrie³

et al. 2001

Neuroendocrinology

Self Cite

Estrogen receptor α (ERα) is the predominant estrogen receptor subtype in the anterior pituitary gland. In order to assess the influence of the pure antiestrogen EM-652.HCl on ERα gene transcription, we have studied the effect of long-term administration of the antiestrogen in ovariectomized rats as well as in intact female rats treated or not with the GnRH-agonist D-trp⁶, des-Gly-NH₂¹⁰ GnRH ethylamide (GnRH-A), a treatment which induces pharmacological castration. To evaluate the degree of pituitary responsiveness to changes in estrogen exposure, prolactin (PRL) mRNA levels were also measured. ERα and PRL mRNA levels were evaluated by quantitative in situ hybridization. It was found that, 49 weeks after ovariectomy (OVX), pituitary ERα mRNA levels were decreased by 55%. Long-term administration (49 weeks) of EM-652.HCl to OVX animals resulted in a further 41% decrease in ERα mRNA. On the other hand, ovariectomy induced an 82% decrease in PRL mRNA levels while the administration of EM-652.HCl to OVX animals did not further decrease PRL mRNA. The administration of EM.652.HCl or GnRH-A alone to intact rats during 52 weeks did not significantly modify pituitary ERα mRNA levels. Concomitant administration of both GnRH-A and EM-652.HCl induced 41 and 47% decreases in ERα mRNA levels, when compared to the levels measured in vehicle-treated and GnRH-treated animals respectively. Combined administration of EM.652.HCl and GnRH-A induced 56 and 65% decreases in PRL mRNA, respectively. When EM-652.HCl was administered concomitantly with GnRH-A, the inhibitory effect on PRL mRNA levels was more marked than that observed in GnRH-A-treated animals. The present data demonstrate that when circulating estrogens are absent or maintained at very low levels by GnRH administration, EM-652.HCl can still depress ERα gene transcription. It is suggested that estrogens can positively regulate pituitary ERα gene transcription and that the antiestrogen EM-652.HCl can downregulate by itself pituitary ERα gene transcription.

Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Effect of Long-Term Treatment with the Antiestrogen EM-652.HCl on Pituitary Estrogen Receptor Alpha and Prolactin mRNA Expression in Intact, Ovariectomized and Gonadotropin- Releasing Hormone-Treated Female Rats

El‐Alfy²,

Labrie³

et al. 2001

Neuroendocrinology

Self Cite

“…In the male and female rat pituitary, two PRL cell types have been characterized by electron microscopy: the typical PRL cell type (type 1) which contains large irregularly shaped secretory granules and another cell type which contains only small round granules (type 2) [9, 10, 11]. In both male and female rats, type 1 PRL cells are much more abundant than type 2 cells, while, in the mouse pituitary, type 2 PRL cells have not so far been described [12, 13, 14].…”

Section: Introductionmentioning

confidence: 99%

Morphological Studies of Prolactin-Secreting Cells in Estrogen Receptor α and Estrogen Receptor β Knockout Mice

Phaneuf

et al. 2003

Neuroendocrinology

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Estrogens play a major role in the regulation of prolactin (PRL) secretion through activation of pituitary and hypothalamic estrogen receptors (ERs). In order to evaluate the relative role of ERα and ERβ in the control of PRL density in the pituitary gland, we performed immunocytochemical localization of PRL and ERs in pituitaries of wild-type (WT), ERα knockout (KO) and ERβKO mice. In WT and ERβKO anterior pituitaries, the vast majority of secretory cells contained ERα immunoreactivity, while no ERα immunostaining could be found in ERαKO pituitaries. No ERβ immunoreactivity could be detected in pituitaries of WT, ERαKO or ERβKO mice. At the light microscopic level, a large number of cells staining for PRL were present in pituitaries of female WT, while in female ERαKO pituitaries, the density of PRL cells was much lower. In WT male pituitaries, the density of PRL cells was lower than observed in female WT, while PRL staining was markedly decreased in male ERαKO as compared to male WT. In ERβKO mice of both sexes, the results were identical to those observed in WT animals. At the electron microscopic level, in WT mice of both sexes, type 1 PRL cells exhibited a well-developed Golgi apparatus and a large number of strongly stained large mature and immature secretory granules. Type 2 PRL cells were also present in the pituitary. Type 2 PRL cells contain small poorly labelled granules. In ERαKO mice of both sexes, type 1 PRL cells were atrophied with poorly developed Golgi apparatus, and no type 2 PRL cells could be observed. In ERαKO pituitaries, typical gonadectomy cells were found. No ultrastructural changes were observed in PRL cells of ERβKO mice. The present data strongly suggest that the positive regulation of PRL expression at the pituitary level by estrogens is mediated by ERα and does not involve ERβ activation.

“…The absence of significant effects of BRO in the intact male rat does not correlate with previous data on PRL release which indicated that chronic injection of BRO can induce a decrease in plasma PRL levels (I, 3). This might be due to a lack of sensitivity of our quantitative technique or to an effect of BRO which in the (9,12). intact animal might occur on the release rather than on the gene expression of PRL.…”

Section: Discussionmentioning

confidence: 99%

“…DA agonists have also beeti shown to inhibit the transcription of the PRL gene in vitro (4). On the other hand, administration of 17Lj-estradiol (E,) resultcd in an increase of PRL gene expression in vivo as well as in l / / r o (2,(5)(6)(7)(8)(9). Furthermore, in vitro studies have shown that estt-ogens can lead to a marked reversal of the potent effect of D A iigonists on PRL release (10,11) as well as on the transcription of the PRL gene (6).…”

mentioning

confidence: 99%

In vivo Regulation of Prolactin Gene Expression in the Male Rat: Role of Sex Steroids and Dopamine

Tong

1991

J Neuroendocrinology

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Can vla Key ~o rd s pro I ac t i n , ha I o pe r i d o I, es t rad i o I, d I h y d rot es t 0 s t e ro ne, b ro m oc r i p t i n e AbstractThe influence of sex steroids and the dopaminergic system on the in vivo modulation of prolactin (PRL) mRNA levels was investigated by quantitative in sifu hybridization in the male rat anterior pituitary gland. In sifu hybridization was performed using a [35SS]-labeled cDNA probe encoding PRL. Orchiectomy performed 14 days earlier did not modify PRL mRNA levels. In orchiectomized rats treatment with the dopaminergic agonist bromocriptine for 14 days decreased PRL mRNA levels by 30%, while in intact animals the same treatment did not induce any changes in PRL mRNA levels. Administration of the dopamine D, receptor antagonist haloperidol in both intact and orchiectomized rats induced a 4-fold increase in mRNA levels. Administration of dihydrotestosterone to orchiectomized animals which had been treated or not with haloperidol or bromocriptine did not modify PRL mRNA levels. In orchiectomized animals administration of l7fl-estradiol (0.25pg twice daily) for 14 days caused a 4-fold increase in amounts of PRL mRNA. Administration of bromocriptine to 17fl-estradiol-treated animals induced a 15% decrease of PRL mRNA levels compared to those obtained by 17/&estradiol administered alone. The concomitant administration of 17/bestradiol and haloperidol resulted in a 50% increase in PRL mRNA levels compared to those measured in animals treated with haloperidol alone. The present results clearly demonstrate that in vivo estrogen as well as dopamine-mediated mechanisms play a regulatory role in PRL mRNA levels in the male rat Proixtin (PRL) gene expression and secretion are positively and neg;:: ively regulated by several hormones. The most important regLilator appears to be dopamine (DA) which is secreted by hypothalamic neurons and sex steroids, especially estrogens and andit,gens, which are produced by the gonads ( I , 2). Much evitlimce obtained in the rat suggests that DA secreted by the tuber-oinfundibular system is the main inhibitory factor involved in thc control of PRL secretion (1, 3 ) . DA agonists have also beeti shown to inhibit the transcription of the PRL gene in vitro (4). On the other hand, administration of 17Lj-estradiol (E,) resultcd in an increase of PRL gene expression in vivo as well as in l / / r o (2, 5-9). Furthermore, in vitro studies have shown that estt-ogens can lead to a marked reversal of the potent effect of D A iigonists on PRL release (10, 11) as well as on the transcription of the PRL gene (6). Recently, we have shown that the nonarornatizable androgen dihydrotestosterone (DHT) could reverse the \timulatory effect of E, on PRL mRNA levels in castrated male rats (8).In order to better understand the in vivo interactions between DA and sex steroids in the regulation of PRL gene expression, we have studied the effects of the dopaminergic agonist bromocriprine (BRO) and the DA D, receptor antagonist haloperidol (HAL) administered alone or in combination w...