Biomedical subjects

L Cattaneo

Publications and source records attributed to L Cattaneo.

33 records · Page 2Linked to original sources

PubMed1996

Sixteen weeks of hexarelin therapy in aged dogs: effects on the somatotropic axis, muscle morphology, and bone metabolism.

Hexarelin (HEXA; 500 micrograms/kg/die, s.c.) was administered for 16 weeks to six old beagle dogs. The treatment consisted of three on-drug periods spaced by two off-drug periods. During each on period, the growth hormone (GH) peak response to HEXA initially increased and then dropped to pretreatment values. Each time, a wash-out interval restored the same pattern of GH responsiveness. HEXA significantly augmented the indices of spontaneous pulsatility of GH, but plasma insulin-like growth factor I levels did not change during treatment. HEXA apparently reduced bone resorption since it significantly decreased the urinary concentration of lysylpyridinoline, a bone matrix component. Bone formation apparently was not affected since unchanged levels of alkaline phosphatase were recorded. In three of six old dogs, HEXA induced an improvement of some morphological and biochemical muscular indices, evaluated in muscle specimens that, instead, remained unchanged in a group of young untreated controls. These findings indicate that HEXA effectively releases GH and primes the pituitary of old dogs, and strengthen the view that in aging, GH secretion may be restored by pharmacological means. It would also appear that HEXA-induced GH release improves some indices of body composition in old dogs.

Animals↗

PubMed1996

In vivo microdialysis of the hypothalamus: a suitable method to study the function of hypophysiotropic neurons in the rat.

Brain microdialysis is a method commonly exploited by neuropharmacologists to study the mechanism of action and preclinical features of centrally acting drugs. It allows measurement of chemical messengers released into the extracellular space, providing a first approximation of neuronal function in selected areas. In this study we have applied the microdialysis of the hypothalamus to evaluate the release of somatostatin from neurosecretory neurons which are involved in growth hormone regulation and validated this method with different challenges.

Animals↗

PubMed1996

Somatostatin withdrawal as generator of pulsatile GH release in the dog: a possible tool to evaluate the endogenous GHRH tone?

Reportedly, somatostatin (SS) withdrawal is an effective generator of pulsatile GH release in mammals and it has been proposed that the amplitude of the GH bursts is related to the functional activity of GHRH-producing neurons. Our study was designed to test this hypothesis in the unanesthetized dog, under different conditions of endogenous GHRH function. First, we evaluated the ability of withdrawal of SS infusion to induce a GH secretory burst under basal conditions when GHRH function is thought to be enhanced, i.e. in young (2- to 3-year-old) dogs under sustained (30 days) caloric restriction (CR) or a 2-day fast. Secondly, we performed experiments in aged (11- to 17-year-old) dogs, in which hypothalamic GHRH secretion is thought to be reduced. Old dogs were evaluated under basal conditions, after a 2-day fast and after a 10-day administration of GHRH alone or followed by fasting. Both before and 14 h after the end of each experimental period, young and old dogs underwent a 3-hour (from 10.00 to 13.00 h) intravenous SS infusion (4 micrograms.kg-1.h-1). The secretory profile of GH was generated by 15-min sampling from 09.00 to 15.00 h. Under baseline conditions, SS withdrawal induced a significant burst of GH in young but not in old dogs. After CR, termination of SS infusion was followed in young dogs by a robust GH burst, significantly higher than that observed when dogs were fed ad libitum. In this instance, reduction of plasma IGF-I concentrations was unlikely to be responsible for the higher GH burst; the same pattern was present in the young dogs after a 2-day fast, when circulating IGF-I was unaltered. In old dogs, SS withdrawal did not modify baseline GH levels even after fasting, but induced a significant GH increase after GHRH priming. When GHRH priming was followed by fasting, SS withdrawal resulted in a GH burst higher than that occurring after fasting or GHRH alone. Altogether, these data support the view that the rebound rise in GH induced by withdrawal of SS is related to the endogenous GHRH tone. It is suggested that extrapolation of these findings to humans might permit probing, albeit inferentially, the endogenous GHRH tone under different physiologic or pathologic conditions.

Animals↗

PubMed1996

Characterization of the hypothalamo-pituitary-IGF-I axis in rats made obese by overfeeding.

Obesity is coupled to several disturbances of the endocrine axes. It has previously been shown that genetically obese Zucker male rats have an impaired secretion of growth hormone (GH), probably originating from a primary reduction of hypothalamic GH-releasing hormone (GHRH) function and resulting in a decrease of GH gene expression and release. We sought to evaluate the somatotropic function in another model of experimental obesity. Normal male Sprague-Dawley rats were fed an energy-rich highly palatable diet for 7 months until they reached body weights overlapping those reported for obese Zucker rats. They were then evaluated for different indices of the hypothalamo-pituitary-somatomedin-C (IGF-I) axis. At the end of the overfeeding period, rats were divided into overtly obese (obese group) and overweight (overweight group) rats according to the degree of overweight and the Obesity Lee Index, while rats fed ad libitum with the standard pellet chow served as controls. Acute administration of a supramaximal dose of GHRH (2 micrograms/rat i.v.) elicited a significantly (at least P < 0.05) lower plasma GH rise in the overweight and obese groups compared with the controls although no difference was seen in the pituitary GH content and gene expression and plasma concentrations of free IGF-I in the two experimental groups vs the controls. In addition, evaluation of hypothalamic GHRH and somatostatin mRNAs (slot-blot hybridization) did not show any significant differences between the three groups. Of the different metabolic indices investigated, plasma glucose and insulin concentrations were significantly (P < 0.01) higher in the obese than in the overweight and control groups. A sharp decrease in plasma testosterone levels, together with a reduction in testis weight, was seen in both groups of rats fed the palatable diet compared with the controls. These findings underline the 'peripheral' feature of the hyposomatotropinism of rats chronically fed an energy-rich diet, and may account for the reversibility of the GH impairment in many obese subjects once a normal body weight has been restored. Moreover, the peripherally-driven hyposomatotropinism of these rats is in sharp contrast with the hypothalamic-driven GH secretory impairment of the obese Zucker rats.

Animals↗

PubMed1993

Effect of acute and short-term administration of cholinomimetic drugs on corticosterone secretion in the rat.

Centrally acting cholinomimetic drugs have been proposed for the therapy of cognitive disorders in aged subjects. Among the possible adverse side effects of this class of compounds, of great relevance is the stimulatory action on the adrenocortical axis, in view of the toxicity of glucocorticoids for hippocampal neurons and the immune system. The aim of the present study was to evaluate in conscious male rats the effect of acute and short-term administration of three novel cholinomimetic drugs on the release of corticosterone. The potent agonist of muscarinic receptors RU 35963 strikingly increased corticosterone levels after acute but not after short-term (6 days) administration. Similar results were obtained after administration of the reversible inhibitor of cholinesterase, eptastigmine. In contrast to RU 35963 and eptastigmine, acute administration of a choline precursor, L-alpha-glycerylphosphorylcholine, only slightly affected plasma corticosterone concentrations after both acute and short-term administration. It is concluded that activation of adrenocortical function by cholinomimetic drugs is a short-lasting event which does not represent an important side effect of these compounds when given on a long-term basis.

Analysis of Variance↗

PubMed1993

Growth hormone secretion is differently affected in genetically obese male and female rats.

Growth hormone (GH) secretion is markedly blunted in obesity. Reportedly, genetically obese Zucker rats show a reduced GH secretion due to an impaired function of hypothalamic neurons producing the GH-releasing hormone (GHRH). The aim of this work was: (1) to compare the in vitro GH responsiveness to GHRH in genetically obese female versus male Zucker rats and, (2) to evaluate the function of hypothalamic GHRH and somatostatin and of pituitary receptors for these neurohormones as assessed by the effectiveness of GHRH and somatostatin on adenylate cyclase (AC) activity. Baseline GH secretion of pituitaries obtained from male and female obese rats was not different and similar to that present in lean counterparts. Stimulation with 10(-7) M GHRH elicited a significantly lower GH secretion from the pituitaries of obese male rats but induced a similar GH secretion from the pituitaries of lean and obese female rats. In these pituitaries, GH concentration was similar in obese versus lean male and female rats [corrected]. A sex-related difference was also evidenced when plasma concentrations of somatomedin C (IGF-I) were evaluated. Obese male rats had lower IGF-I concentrations than lean counterparts, while this was not the case for obese versus lean female rats. Evaluation of AC activity following GHRH disclosed a lower activation in obese than in lean male rats, whereas in the females the enzyme activation was higher in obese than in lean animals. Conversely, the inhibitory effect of somatostatin on forskolin-stimulated AC was similar in pituitary membranes of obese and lean rats of both sexes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗

PubMed1971