Past Issue

Volume 19, Number 3, Oct-Dec (Autumn) 2017, Serial Number: 75 Pages: 461-468

Effects of Estradiol on Histological Parameters and Secretory Ability of Pituitary Mammotrophs in Ovariectomized Female Rats

Nataša Ristić, Ph.D, 1, *, #, Vladimir Ajdžanović, Ph.D, 1, *, #, Milica Manojlović-Stojanoski, Ph.D, 1, Jovana Maliković, M.Sc, 1, Gordana Ušćebrka, Ph.D, 2, Zorica Marković, M.Sc, 3, Verica Milošević, Ph.D, 1,
Department of Cytology, Institute for Biological Research "Siniša Stanković", University of Belgrade, Belgrade, Serbia
Department of Veterinary Medicine, Faculty of Agriculture, University of Novi Sad, Novi Sad, Serbia
Clinical Centre "Dr Dragiša Mišović", Belgrade, Serbia
*Corresponding Address: Department of Cytology Institute for Biological Research "Siniša Stanković" University of Belgrade 142 Despot Stefan Blvd. 11060 Belgrade Serbia,

The first two authors equally contributed to this manuscript.



Estrogen replacement therapy remains current as a therapeutic approach to treat menopausal symptoms and may significantly affect hormone-producing cells in the female pituitaries. The aim of this study was to examine the histological parameters of pituitary mammotrophs and prolactin secretion after chronic estradiol treatment in ovariectomized adult female rats, reflecting premature menopause.

Materials and Methods

In this experimental study, adult female Wistar rats were divided into non-ovariectomized (C), ovariectomized (OVX) and estradiol-treated ovariectomized (OVX+E) groups. Estradiol dipropionate [0.625 mg/kg body mass per day] was administered for four weeks, while the C and OVX groups received vehicle alone. Mammotrophs were identified by the peroxidase-antiperoxidase (PAP) immunohistochemical procedure, while prolactin concentrations were measured by the non-isotopic two-step assay (Delfia) method. Comparison of the differences between groups was performed using one-way analysis of variance (ANOVA) and Tukay (honest significant difference) HSD test.


Ovariectomy caused significant (P<0.05) decreases in mammotroph optical density (OD), volume density (VV) and number per mm2 by 29, 27 and 34%, respectively, in comparison with the C females. In the OVX+E group, significant (P<0.05) increases in OD, cell volume, VVand number of mammotrophs per mm2 by 181, 15%, 5.8-fold and 5.2-fold, respectively, were observed when compared to OVX animals. The serum prolactin concentration in OVX females was significantly (P<0.05) decreased by 14% in comparison to the C group, while in OVX+E females, prolactin levels were significantly (P<0.05) increased by 53% compared to the OVX controls.


Estradiol supplementation in ovariectomized females is followed by stimulatory histological and secretory changes of the mammotrophs. These results could serve as indicators of possible prolactinome development upon estradiol application in premature menopausal subjects.