MORPHOLOGICAL-CHANGES IN THE PITUITARY-GLAND OF DOGS CHRONICALLY EXPOSED TO EXOGENOUS GROWTH-HORMONE

Growth hormone (GH) synthesis and release from the pituitary is regula ted by hypothalamic releasing hormone, insulin-like growth factor-1 (I GF-1), and somatostatin. However, the potential effects of pharmacolog ical doses of exogenous GH on the pituitary are not well studied. To d etermine the potential chronic effects of exogenous GH on pituitary mo rphology in dogs, porcine GH (pGH) was administered subcutaneously to 3 groups of dogs (4 animals/sex/group) at doses of 0.025, 0.1, and 1.0 IU/kg/day for 14 wk. A group (4/sex) of dogs served as the vehicle co ntrol. The pituitaries from all dogs were weighed and fixed in appropr iate fixatives for light and electron microscopic examination; in addi tion, cells of the pars distalis were quantitated by a point counting method following immunostaining to identify cells containing GH, prola ctin (PRL), and adrenocorticotrophic (ACTH) hormones. Administration o f pGH resulted in a statistically significant (p less than or equal to 0.05) increased pituitary weight through the high dose. By light micr oscopy (LM), hypertrophy of pars distalis cells was evident in mid-and high-dose female dogs. The pituitaries of dogs given the lowest dose (0.025 IU/kg/day) of pGH were not remarkable based on weight and LM fi ndings. In addition, transmission electron microscopic (TEM) examinati on of the pituitary gland of high-dose dogs demonstrated, in both sexe s, pituitary cells with variably dilated rough endoplasmic reticulum a nd decreased numbers of secretory granules; some of these cells reacte d positively to GH immunostaining. Quantitative analysis of the pituit ary gland of high-dose males and females showed an increase in the abs olute volume of all cell populations studied: GH-, PRL-, and ACTH-posi tive cells. Based on the LM and TEM findings, the increased volume of the cell populations studied is likely related to cellular hypertrophy . The expected elevation in serum GH levels following repeated adminis tration of pGH and an associated elevation in serum IGF-1 levels resul ted in morphologic changes in the pituitary gland of dogs given high d oses (greater than or equal to 0.1 IU/kg/day) of pGH; these observatio ns differed from the reported findings in pituitaries of transgenic mi ce secreting large quantities of bovine GH.