Modern Approaches to Classification of Pituitary Tumors in Human Subjects and Animals

Historical control background incidence of spontaneous pituitary gland lesions of Han-Wistar and Sprague-Dawley rats and CD-1 mice used in 104-week carcinogenicity studies

“…This speculation was supported by this study, in which the incidences of mammary tumors were 10.70% in Han-Wistar rats (males, 0.11%, and females, 21.26%) and 39.28% in Sprague-Dawley rats (males, 2.10%, and females, 76.35%), respectively. Also, both strains of rats and the CD-1 mice exhibited a marked sex predisposition, with females more commonly affected for adenoma and/or carcinoma of the pars distalis, which is in line with the previous literature 6 . This higher incidence of pituitary tumors in females suggests that estrogen is involved, either by a direct effect on the pituitary gland or inhibition of dopamine 27 .…”

“…As reported by previous studies, spontaneous proliferative lesions of the pituitary gland are more common in rats than mice 19 . In rats, the frequency increases with age in all strains, and the tumors usually begin to appear between 13 and 24 months of age 6 . Primary proliferative lesions of the pituitary are, as is well known, most frequently found in the pars distalis and are rarely encountered in the pars intermedia or pars nervosa 20 , 21 , 22 , 23 .…”

“…Proliferative lesions of the pituitary can be induced in rodents by several compounds, irradiation, or high caloric/protein diet 1 , 2 , 3 . Among these compounds, estrogenic agents are well known to cause prolactin (PRL) cell hyperplasia and eventually induce pituitary neoplasia via sustained stimulation with estrogens 4 , 5 , 6 . Compounds which alter the normal pituitary-target organ axis can also secondarily induce proliferative pituitary lesions by hyperstimulatory mechanisms due to altered feedback regulation.…”

“…Compounds which alter the normal pituitary-target organ axis can also secondarily induce proliferative pituitary lesions by hyperstimulatory mechanisms due to altered feedback regulation. For instance, anti-thyroid compounds cause decreased T3/T4 levels in the blood due to disruption of thyroid function, followed by increased thyroid-stimulating hormone (TSH) levels via the negative feedback mechanism of the pituitary-thyroid axis, which result in TSH-producing cell (thyrotroph) hyperplasia 6 , 7 . Although proliferative lesions of the pars intermedia are rare compared with those induced in the pars distalis, there are some reports indicating that haloperidol, a dopamine receptor antagonist, can cause diffuse hyperplasia in the pars intermedia 8 , 9 .…”

The Effects of Ad Libitum Overfeeding and Moderate and Marked Dietary Restriction on Age-Related Spontaneous Pituitary Gland Pathology in Sprague—Dawley Rats

“…Serum PRL levels were generally elevated in groups 1, 2, and 3, where the incidence of tumors was elevated, while in group 4 serum PRL levels and pituitary tumor incidence were low. Chronic elevation of circulating PRL is thought to be involved in the pathogenesis of spontaneous pituitary tumors (46,61). With aging, there is a loss of dopaminergic neurons in the hypothalamus of rats (11), which results in decreased dopamine secretion and lower releases of GH and LH releasing and PRL inhibiting factors (11,50,55,57).…”