Magnetic resonance imaging compared with hormonal effects and histopathology of estrogen-induced pituitary lesions in the rat.
Estrogen-induced pituitary lesions in rats were studied in time-sequence experiments using magnetic resonance imaging (MRI), hormone determinations and light microscopy. The main purpose of the study was to evaluate the usefulness of MRI in comparison with conventional biochemical and histopathological methods for detecting the pituitary lesions as early as possible and to follow their development. Measurements were made at 15 time points, ranging from 1 h to 272 days after s.c. implantation of the estrogen pellet. High-resolution T1 weighted sagittal images with 2 mm slice thickness were made with a 2 Tesla 30 cm small-bore MRI system. Radioimmunoassay (RIA) was used to determine the different pituitary hormones. Conventional histopathology and immunoperoxidase staining methods were used to characterize the pituitary lesions and visualize the hormone-producing pituitary cells respectively. The first histopathological pituitary changes (enlarged acidophilic cells with increased number of vacuoles) were seen at day 2 after initiation of the estrogen treatment, while at day 4 the first immunohistochemical changes (increased number of prolactin-positive cells) were encountered. Significantly increased prolactin levels in blood plasma occurred from day 9 onwards. Also at day 9, changes of the pituitary gland were first visible on MR images, showing rounding of the anterior edge of the gland. Gradual enlargement of the pituitary caused by hyperplasia of hypertrophic prolactin-positive cells could be followed by MRI, and later on pituitary tumors were recognized, their images being heterogeneous due to great differences in signal intensity ranging from hypo- or iso- to hyperintense. Signal intensities of hemorrhagic tumor areas varies widely due to variation in the blood flow maintained in these areas. In was concluded that MRI is a powerful tool for detecting enlargement and tumors of the pituitary gland in rats. This method allows the development of such lesions to be followed in one and the same animal, thereby reducing the need of interim kills and thus the number of animals to be used.
van Nesselrooij
J H
JH
Department of Biological Toxicology, TNO-CIVO Toxicology and Nutrition Institute, Zeist, The Netherlands.
Bruijntjes
J P
JP
van Garderen-Hoetmer
A
A
Tillapaugh-Fay
G M
GM
Feron
V J
VJ
D000818:Animals; D004958:Estradiol / Q000008:administration & dosage / Q000633:toxicity; D004967:Estrogens / Q000633:toxicity*; D007279:Injections, Subcutaneous; D008279:Magnetic Resonance Imaging; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects / Q000473:pathology; D010907:Pituitary Hormones / Q000097:blood; D010911:Pituitary Neoplasms / Q000097:blood / Q000139:chemically induced / Q000175:diagnosis* / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D004967:Estrogens; D010907:Pituitary Hormones; D004958:Estradiol