Local action of intrahypophyseal implants of estrogen as revealed by staining with peroxidase‐labeled antibody

Abstract

The direct action of 17 p-estradiol and cholesterol on cells of the pituitary pars distalis, as revealed by staining with peroxidase-labeled antibody, was studied in female rats. Pellets of pure cholesterol and of estradiol mixed with cholesterol were implanted into the left lobe of the pars distalis 14-32 days after ovariectomy and left in place for 7-16 days. Rabbit antisera to rat prolactin, human growth hormone, human chorionic gonadotropin (for gonadotropes -presumably luteinizing hormone cells), and porcine corticotropin were used. In no case were cells altered in the contralateral lobe of the pars distalis; cholesterol likewise had no significant effect on the ipsilateral lobe. However, in the ipsilateral lobe containing an estrogen pellet, prolactin cells were hypertrophied and hyperplastic; cells assumed to be responsible for luteinizing hormone secretion were reduced in size and stained more intensely; and growth hormone cells were reduced in size. Corticotropin cells remained unaffected. For the most part estrogenic effects were distributed ventrally, caudally and laterally from the pellet and not far medially, never reaching the midline. It was concluded that estrogen acts directly on the hypophysis, the spread of the effects reflecting the direction of blood flow within the gland. These observations support the hypothesis that the pituitary gland serves as a site for feedback action by estrogen.One of the most important current problems in neuroendocrinology is to ascertain whether the hypothalamus or hypophysis serves as the primary site for feedback action by target-organ hormones. Evidence available at present indicates that both sites are probably responsive to estrogen but the manner in which the functional roles of the hypothalamus and hypophysis are integrated remains unclear.Several investigators have implanted ovarian tissue or estrogen into the hypothalamus and, from the effects observed, concluded that estrogens act primarily on the hypothalamus. Thus, Flerko and Szentitgothai ('57) found that ovarian secretory activity was depressed in rats bearing small intrahypothalamic autotransplants of ovarian tissue, but not in rats bearing intrapituitary implants. Likewise, implantation of estrogen into the median eminence of the rabbit caused depression of ovarian function (Davidson and Sawyer, and elevated the prolactin content of the gland (Kanematsu and Sawyer, '63a). These workers found that estrogen placed into the hypophysis failed to duplicate these effects, the pituitary prolactin content actually being depressed (Kanematsu and Sawyer, 63a).Apparently the rat responds differently to these experimental procedures. After Lisk ('60) showed that estrogen implanted into the hypothalamic arcuate nucleus causes atrophy of the genital tract, McCann and his colleagues found that estrogen located in either the median eminence or hypophysis was effective; such implants prevented the postovariectomy rise in plasma luteinizing hormone (Ramirez Abrams and McCann, '64) and elicited peripheral e...

Chronic effect of antidopaminergic drugs or estrogen on male Wistar rat lactotrophs and somatotrophs

“…The treatment with estrogen increased the percentage of lactotrophs by approxi- (3,(7)(8)(9)(10)(11). In most of these studies, the evaluation was visual and rough and only on two occasions (3,11) was it quantitative or semiquantitative.…”

Direct arterial vascularization of estrogen-induced prolactin-secreting anterior pituitary tumors.

“…The size of the anterior pituitary gland (AP) of estrogen-treated animals is markedly increased, which is associated with increased mitotic activity (4). The primary cells affected are prolactin (PRL)-producing cells, lactotrophs.…”

“…The primary cells affected are prolactin (PRL)-producing cells, lactotrophs. Estrogen stimulates both PRL synthesis and proliferation of lactotrophs (4)(5)(6)(7). Different strains of rats have different susceptibilities to the tumorigenic action of estrogen, with the Fischer 344 strain being particularly sensitive (8,9).…”

Differences between rat strains in the development of PRL-secreting pituitary tumors with long-term estrogen treatment: <i>In vitro</i> insulin-like growth factor-1-induced lactotroph proliferation and gene expression are affected in Wistar-Kyoto rats with low estrogen-susceptibility

“…There is evidence that estrogens induce pituitary growth when pituitaries are transplanted under the kidney capsule [17], and that intrapituitary implants of estrogen induce lactotroph hyperplasia in the ipsilateral lobe containing an estrogen implant but not in the contralateral lobe. These findings suggest that pituitary mechanisms play a dominant role in the action of estrogen on the development of PRL-secreting pituitary tumors [18].…”