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Introduction
Pituitary mammotrophs, i.e. prolactin(PRL) producing cells, in rats are distributed throughout the anterior-ventral part as well as in the areas near the gland pars intermedia (1). Classification of mammotrophs takes secretory granule size as a key criterion and accordingly three types of these cells are identified (1,2). PRL is a pulsatile secreted polypeptide hormone, functionally entwined with ovulation, pregnancy or nursing and characterized by a significant, age-related rise in females (1,3,4). Also, the number of female mammotrophs and their DNA content increase with ageing (5,6). Generally, the intensified PRL release with age is partly due to dysfunction of the dopaminergic mechanism in the hypothalamus (7). Studies in postmenopausal subjects have confirmed these secretory changes as far-reaching, since PRL levels do not decrease in that period of life (8).
Premature menopause, linked with estrogen deficiency and infertility in young women, can develop spontaneously or may be caused by iatrogenic factors (9). A whole range of profound symptoms such as hot flashes, bone deterioration, decreased libido, cardiovascular issues and depression are included into its manifestation (9,10). When it comes to the mammotroph function in premature menopausal females, it was found long ago that PRL levels remain within normal range, while the pulsatility of secretion flattens (11). Estrogen replacement therapy is a common therapeutic approach to treat menopausal symptoms, with confirmed effectiveness in osteoporosis treatment (12), but due to possible adverse effects (breast or endometrial cancer, thromboembolic events) careful selection of dosage and duration of use are advised (13,15).
Literature data have already pointed out that estradiol potently influences mammotroph differentiation, function and proliferation in vitro (16), while its effects in prematurely menopausal females remain insufficiently elaborated. Since estradiol application in menopausal subjects may change the histological parameters of pituitary mammotrophs and PRL secretion, our aim was to explain the phenomenology of potential estradiol-caused changes in ovariectomized adult female rats using modern histological and biochemical methodologies. Thus, in our model reflecting premature natural/iatrogenic menopause, we investigated the immunohistomorphometric characteristics of pituitary mammotrophs, using a design-based stereological approach, as well as their secretory ability, by measuring the optical density (OD) of immunostaining and the circulating PRL levels (17,18).
Materials and Methods Experimental design
In this experimental study, 21 female Wistar rats 12-weeks old (with the average body mass...