Search Results
You are looking at 1 - 10 of 20 items for
- Author: E. E. Müller x
- Refine by access: All content x
Search for other papers by A. PECILE in
Google Scholar
PubMed
Search for other papers by E. MÜLLER in
Google Scholar
PubMed
SUMMARY
The effect of cortisol (5 mg./100 g. body weight administered for 10 days) on the secretion of growth hormone (GH) from the pituitary was studied in 30-day-old female rats. The results indicate that the suppressive action of cortisol on GH secretion is not due to a reduced availability of the hormone in the pituitary but to an impairment of the release mechanism(s) as shown by the lack of GH release in response to insulin hypoglycaemia and by the marked decrease of GH-releasing activity in the hypothalamus of cortisol-treated rats.
Search for other papers by E. E. Müller in
Google Scholar
PubMed
Search for other papers by V. Locatelli in
Google Scholar
PubMed
Introduction
Interest in anorexia nervosa (AN) has grown remarkably in recent years, the surge of interest in public attention probably reflecting an increase in the incidence of the disease. Recent studies have found, in fact, that AN may affect as many as 0·8% of particularly susceptible groups, such as middle-class, late-adolescent girls (Culberg & Engstrom-Lindberg, 1988). From a clinical viewpoint the disease is characterized by an autoinduced starvation due to a relentless and pathological pursuit of thinness, a distortion of body image, unusual food-related behaviours and amenorrhoea.
In the disease, psychological, biological, familial and sociocultural factors are thought to be important for the development and expression of the behavioural aberrations, even though the relative contribution of each factor may be different among a heterogenous population of subjects.
Among the biological abnormalities which characterize AN, a major role is that taken by the neuroendocrine abnormalities and a major issue has been
Search for other papers by M. Parenti in
Google Scholar
PubMed
Search for other papers by D. Cocchi in
Google Scholar
PubMed
Search for other papers by G. Ceresoli in
Google Scholar
PubMed
Search for other papers by C. Marcozzi in
Google Scholar
PubMed
Search for other papers by E. E. Müller in
Google Scholar
PubMed
ABSTRACT
The mechanisms underlying the age-related decrease and increase in somatotroph responsiveness to growth hormone-releasing factor (GHRF) and somatostatin respectively were studied in rat pituitary membranes in vitro.
Basal adenylate cyclase (AC) activity was similar in pituitary membranes from rats of 8 days (either sex) and male rats of 3 months, but it was almost threefold higher in membranes from male rats of 21–23 months. GHRF induced a lower percentage stimulation of AC activity in membranes from infant and old than adult rats. Somatostatin inhibited stimulation of AC induced by forskolin more effectively in membranes from adult than infant and old rats. In parallel experiments, since the tissue we used is formed by a mixed population of pituitary cells, we evaluated, for comparison, the effect on AC of neurohormones, i.e. vasoactive intestinal polypeptide (VIP) and dopamine which act primarily on lactotrophs. VIP induced a lower fold-stimulation of AC activity in membranes from infant and old than adult rats. Dopamine inhibited forskolin-induced stimulation of AC in the following rank order of magnitude: old, adult and infant rats, and was also more effective in inhibiting basal AC activity in old than in adult rats. The stimulatory and inhibitory G proteins (Gs and Gi) coupled to AC were measured indirectly by evaluating stimulatory and inhibitory effects of different concentrations of GTP on AC. GTP, at stimulatory concentrations, increased AC activity in membranes from infant and adult rats similarly whereas its effect was significantly greater in membranes from old rats. Conversely, GTP, at inhibitory concentrations, decreased AC activity similarly in membranes from adult and infant rats, whereas in old rats inhibition was apparent at more than a tenfold lower concentration of GTP.
These data suggest (1) that the greater somatotroph sensitivity to GHRF in terms of GH secretion of the early postnatal period is not due to supersensitive GHRF receptors but rather may be accounted for, at least partially, by the low function of somatostatinergic receptors; (2) that the inability of GHRF to stimulate GH release in aged rats probably results from an uncoupling between the GHRF receptor and the G protein; and (3) that in aged rats the decreased ability of somatostatin to inhibit AC activity, in spite of the high Gi activity, results from a reduced number of somatotroph cells and, hence, receptors.
Journal of Endocrinology (1991) 131, 251–257
Search for other papers by A. PECILE in
Google Scholar
PubMed
Search for other papers by E. E. MÜLLER in
Google Scholar
PubMed
Search for other papers by M. FELICI in
Google Scholar
PubMed
Search for other papers by C. NETTI in
Google Scholar
PubMed
Search for other papers by D. COCCHI in
Google Scholar
PubMed
SUMMARY
Injections of insulin (0·2 or 0·01 i.u./20 μl) into the lateral ventricle of the rat brain, while not changing blood glucose levels or altering the pituitary content of growth hormone (GH), blocked the release of GH from the pituitary and the decrease of growth-hormone releasing activity (GHRF) of stalk median eminence (SME) extracts in the presence of the hypoglycaemic effect on insulin (2 i.u./kg) given intraperitoneally. Intraventricular administration of insulin also impaired the GH release elicited by cold exposure (4 °C, 1 h) but not the release induced by electric shock. The possibility that insulin injected into the brain acts on glucose-sensitive GH-regulating structures is suggested.
Search for other papers by V. Locatelli in
Google Scholar
PubMed
Search for other papers by A. Torsello in
Google Scholar
PubMed
Search for other papers by M. Redaelli in
Google Scholar
PubMed
Search for other papers by E. Ghigo in
Google Scholar
PubMed
Search for other papers by F. Massara in
Google Scholar
PubMed
Search for other papers by E. E. Müller in
Google Scholar
PubMed
ABSTRACT
Recently, data have been presented showing that muscarinic cholinergic agonists or antagonists can modulate, in opposite ways, GH-releasing hormone (GHRH)-induced GH release in man. The aim of the present study was, first, to confirm these findings in the rat and, secondly, if confirmed, to investigate the mechanism(s) subserving the effect of cholinergic drugs.
In adult male rats bearing chronic indwelling atrial cannulae, pretreatment with the cholinergic antagonists pirenzepine (0·5 mg/kg, i.v.) or atropine (0·5 mg/kg, i.v.) significantly reduced the rise in plasma GH induced by GHRH (2 μg/kg, i.v.), while pretreatment with the cholinergic agonist pilocarpine (3 mg/kg, i.v.) potentiated it. In rats with hypothalamic somatostatin (SRIF) depletion, i.e. rats with anterolateral deafferentation of the mediobasal hypothalamus or rats treated with cysteamine, the modulatory action of cholinergic drugs on the neuroendocrine effect of GHRH was completely lacking. In these two experimental models, an antiserum raised against SRIF failed to elicit a rise in plasma GH and measurement of hypothalamic SRIF content revealed a clear-cut reduction of the neuropeptide. Atropine (1 μmol/l) and pilocarpine (1 μmol/l), added to pituitary cells in vitro, failed to alter GHRH-induced GH release. The present results indicate that muscarinic cholinergic agonists and antagonists modulate GHRH-induced GH release in the rat and suggest that the effect of cholinergic modulation takes place through SRIF.
J. Endocr. (1986) 111, 271–278
Search for other papers by M Rolla in
Google Scholar
PubMed
Search for other papers by A Andreoni in
Google Scholar
PubMed
Search for other papers by D Bellitti in
Google Scholar
PubMed
Search for other papers by M Ferdeghini in
Google Scholar
PubMed
Search for other papers by E Ghigo in
Google Scholar
PubMed
Search for other papers by E E Müller in
Google Scholar
PubMed
Abstract
Previous studies have shown that corticotrophin-releasing hormone (CRH) inhibits GH secretion in response to GH-releasing hormone (GHRH) in normal women and men, and animal studies suggest that this effect is mediated by an increased release of somatostatin from the hypothalamus. It has been reported that there are abnormalities in the neuroendocrine regulation of the hypothalamo-pituitary-somatotrophic axis and the hypothalamo-pituitary-adrenocortical axis in patients with eating disorders. The present study therefore investigated the ability of CRH to inhibit the GH response to GHRH in eight young women with anorexia nervosa (AN) and in seven young women with eating disorders which were not otherwise specified (NOS). We also compared the effect of CRH in the patients with the response it caused in ten control women. In contrast to a previous report, combined i.v. administration of 50 μg human CRH (hCRH) and 50 μg GHRH(1–29) caused a GH response in control women which was higher, although not significantly so, than that induced by GHRH alone (area under the curve (AUC) 988·5 ±506·0 compared with 1568·4 ±795·6 (s.e.m.) ng/ml per 120 min for GHRH alone and GHRH plus hCRH respectively).
Conversely, the administration of hCRH given together with GHRH markedly inhibited the GH response induced by the latter in both AN patients (AUC 2253·0 ±385·7 compared with 1224·4 ±265·7 ng/ml per 120 min for GHRH and GHRH plus hCRH respectively; P<0·005 and NOS patients (AUC 2827·4±281·1 compared with 308·5 ± 183·4 ng/ml per 120 min for GHRH and GHRH plus hCRH respectively; P<0·0001). These results (1) refute the suggestion that there is an inhibitory influence of CRH over GH secretion under normal conditions, (2) indicate that this inhibitory influence exists in patients with eating disorders, and (3) imply that, in the latter, hypothalamic somatostatinergic function is, at least in part, preserved.
Journal of Endocrinology (1994) 140, 327–332
Search for other papers by L Cattaneo in
Google Scholar
PubMed
Search for other papers by V De Gennaro Colonna in
Google Scholar
PubMed
Search for other papers by M Zoli in
Google Scholar
PubMed
Search for other papers by E E Müller in
Google Scholar
PubMed
Search for other papers by D Cocchi in
Google Scholar
PubMed
Abstract
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 μg/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.
Journal of Endocrinology (1996) 148, 347–353
Search for other papers by F. Petraglia in
Google Scholar
PubMed
Search for other papers by V. Locatelli in
Google Scholar
PubMed
Search for other papers by A. Pen̄alva in
Google Scholar
PubMed
Search for other papers by D. Cocchi in
Google Scholar
PubMed
Search for other papers by A. R. Genazzani in
Google Scholar
PubMed
Search for other papers by E. E. Müller in
Google Scholar
PubMed
ABSTRACT
The effect of acute administration of the opioid receptor antagonist naloxone hydrochloride (5 mg/kg, s.c.) on plasma LH levels was evaluated in female and male rats 24, 36 and 48 h and 1,3 and 5 weeks after gonadectomy and in 5-week gonadectomized rats after acute or chronic (2 weeks) administration of oestradiol benzoate (OB, 10 μg/rat per day, s.c.), testosterone propionate (TP, 150 μg/rat, s.c.) or dihydrotestosterone propionate (DHT, 150 μg/rat, s.c.) respectively. Concurrent evaluation of plasma LH after administration of LH releasing hormone (LHRH, 1 μg/kg, i.p.) was performed in the same experimental groups.
In rats of both sexes, a significant rise in plasma LH after naloxone was observed in sham-operated and recently gonadectomized rats (24–48 h); in female rats 36 and 48 h after gonadectomy the rise was higher than in controls. One, 3 and 5 weeks after gonadectomy, naloxone failed to stimulate LH release in both female and male rats. In gonadectomized rats undergoing steroid replacement therapy, OB administered 72 h before testing, TP (16 and 72 h) and DHT (16 h) were the most effective in reinstituting the LH response to naloxone. Chronic administration of gonadal steroids did not restore normal LH responsiveness to naloxone. In most experimental groups, LH responses after naloxone were clearly unrelated to pituitary LH responsiveness to LHRH, which indicates that the opioid antagonist was acting via the central nervous system. In conclusion, these results demonstrate that: (1) gonadal steroids are critically important for the inhibitory effect of endogenous opioids on LH secretion to be manifested; (2) inhibition by the opiatergic system on LH secretion is more dependent on a modulatory action of gonadal steroids than on their simple presence or absence.
J. Endocr. (1984) 101, 33–39
Search for other papers by G Tulipano in
Google Scholar
PubMed
Search for other papers by A V Vergoni in
Google Scholar
PubMed
Search for other papers by D Soldi in
Google Scholar
PubMed
Search for other papers by E E Muller in
Google Scholar
PubMed
Search for other papers by D Cocchi in
Google Scholar
PubMed
Leptin produced by adipocytes controls body weight by restraining food intake and enhancing energy expenditure at the hypothalamic level. The diet-induced increase in fat mass is associated with the presence of elevated circulating leptin levels, suggesting the development of resistance to its anorectic effect. Rats, like humans, show different susceptibility to diet-induced obesity. The aim of the present study was to compare the degree of leptin resistance in obesity-prone (OP) vs obesity-resistant (OR) rats on a moderate high-fat (HF) diet and to establish if the effects of leptin on hypothalamo–pituitary endocrine functions were preserved. Starting from 6 weeks after birth, male Sprague–Dawley rats were fed on either a commercial HF diet (fat content: 20% of total calorie intake) or a standard pellet chow (CONT diet, fat content: 3%). After 12 weeks of diet, rats fed on HF diet were significantly heavier than rats fed on CONT diet. Animals fed on HF diet were ranked according to body weight; the two tails of the distribution were called OP and OR rats respectively. A polyethylene cannula was implanted into the right ventricle of rats 1 week before central leptin administration. After 12 weeks of HF feeding, both OR and OP rats were resistant to central leptin administration (10 μg, i.c.v.) (24 h calorie intake as a percent of vehicle-treated rats: CONT rats, 62 [50; 78]; OR, 93 [66; 118]; OP, 90 [70; 120] as medians and 95% confidence intervals (CIs) of six rats for each group). Conversely, after 32 weeks of diet both OR and OP rats were partially responsive to 10 μg leptin i.c.v. as compared with CONT rats (24 h calorie intake as a percent of vehicle-treated rats: CONT rats, 60 [50; 67]; OR, 65 [50; 80]; OP, 80 [60; 98] as medians and 95% CIs of six rats for each group); the decrease of food intake following 200 μg leptin i.p. administration was similar in all the three groups (calorie intake as a percent of vehicle-treated rats: 86 [80; 92] as median and 95% CI). The long-term intake of HF diet caused hyperleptinemia, hyperinsulinemia and higher plasma glucose levels in OP rats as compared with CONT rats. Plasma thyroxine (T4) was lower in all the rats fed the HF diet as compared with CONT. i.c.v. administration of leptin after 32 weeks of diet restored normal insulin levels in OP rats. Moreover, leptin increased plasma T4 concentration and strongly enhanced GH mRNA expression in the pituitary of OP as well as OR rats (180±10% vs vehicle-treated rats). In conclusion, long-term intake of HF diet induced a partial central resistance to the anorectic effect of leptin in both lean and fat animals; the neuroendocrine effects of leptin on T4 and GH were preserved.
Search for other papers by G Tulipano in
Google Scholar
PubMed
Search for other papers by A V Vergoni in
Google Scholar
PubMed
Search for other papers by D Soldi in
Google Scholar
PubMed
Search for other papers by E E Muller in
Google Scholar
PubMed
Search for other papers by D Cocchi in
Google Scholar
PubMed