Abstract
Several pathological (e.g. obesity and chronic hypercortisolism) and non-pathological (e.g. ageing) states in humans are characterized by a reduction in pituitary growth hormone (GH) secretion. Chronic hypercortisolism in humans is also associated with an impaired GH response to various stimuli. Pituitary-dependent hyperadrenocorticism in dogs is not only associated with less
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GH secreted per pulse but also with an impaired response to synthetic growth hormone secretagogues (GHSs) (Chapter 3 and 4). Both basal and stimulated GH secretion as well as circulating insulin-like growth factor-I (IGF-I) concentrations decline with age in several mammalian species. Little is known about how age affects the GH response to GH-releasing stimuli in dogs. In Chapter 5 it is demonstrated that in young dogs, ghrelin - a recently discovered GHS of gastric origin - is a more potent stimulator of GH release than growth hormone-releasing hormone (GHRH) or growth hormone-releasing peptide-6 (GHRP-6). In old dogs, GHRH administration causes higher elevations of plasma GH concentrations than ghrelin or GHRP-6 administration. The GH-releasing capacity of ghrelin decreases with age whereas this decline is considerably lower for stimulation with GHRP-6 or GHRH. Ghrelin and GHRP-6 are specific releasers of GH. They do not stimulate the pituitary-adrenocortical axis nor the release of thyroid-stimulating hormone, luteinizing hormone, or prolactin. The diagnosis of GH deficiency should be based upon the results of a stimulation test because basal plasma concentrations of GH and IGF-I may overlap between pituitary dwarfs and healthy individuals. A ghrelin-stimulation test may be used in the diagnosis of canine pituitary dwarfism (Chapter 6). Through activation of pathways distinct from those needed for GH secretion, ghrelin causes weight gain by increasing food intake and reducing fat utilization. In several mammalian species this gastric peptide seems to play a role in meal initiation. Chapter 7 is a report on investigations on the effects of food intake and fasting in healthy Beagle dogs. Fasting and food intake lead to higher and lower circulating ghrelin concentrations, respectively. During food intake and fasting, the changes in plasma ghrelin concentrations are not associated with similar changes in plasma GH concentrations. During food intake and fasting, circulating insulin and glucose concentrations change reciprocally with the ghrelin concentrations. In dogs, a pre-eminent example of extra-pituitary GH production is the progestin-induced synthesis in the mammary gland. In this species, mammary GH reaches the systemic circulation and may give rise to a syndrome of GH excess. Treatment with medroxyprogesterone acetate (MPA) in healthy control dogs results in a higher basal plasma GH secretion and less GH secreted in pulses compared to dogs with surgically excised mammary gland tissue (Chapter 8). In both healthy dogs and mastectomized dogs, cystic endometrial hyperplasia (CEH) develops after one year treatment with MPA. Thus, progestin-induced mammary-derived GH is not a requirement for the development of CEH. The presence of immunoreactive GH in the cytoplasm of hyperplastic glandular uterine epithelial cells of dogs with CEH suggests that GH may play a role in the pathogenesis of CEH. In Chapter 9, an integral picture of the effects of progestins on the function of the adenohypophysis in the bitch is reported. The effect of MPA on gonadotrophin secretion is confined to follicle-stimulating hormone (FSH) secretion. MPA treatment increases basal plasma FSH concentration during the first months of treatment, while the pituitary FSH response to supra-pituitary stimulation decreases during MPA administration. The results of the study reported in Chapter 10 indicate that the progesterone receptor blocker aglépristone allows for treatment of progestin-induced hypersomatotropism.
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