Biomedical subjects

M Korbonits

Publications and source records attributed to M Korbonits.

42 records · Page 3Linked to original sources

PubMed1996

L-arginine is unlikely to exert neuroendocrine effects in humans via the generation of nitric oxide.

There is now considerable evidence that nitric oxide is an important neuroregulatory agent, but there has been very little investigation of its possible role in neuroendocrine mechanisms in humans. We have investigated the effects of two nitric oxide precursors, L-arginine and molsidomine, under basal conditions on the pituitary hormones growth hormone (GH), prolactin, luteinizing hormone, follicle-stimulating hormone, thyrotrophin, adrenocorticotrophin (ACTH) and vasopressin, and also on serum cortisol; we have also studied the effect of L-arginine on circulating prolactin, ACTH and cortisol in normal human subjects under hypoglycaemic stress. L-Arginine stimulated both GH and prolactin release under basal conditions but had no effect on the other hormones studied, while the nitric oxide donor molsidomine showed no effect on any hormone studied. L-Arginine potentiated the hypoglycaemia-stimulated release of ACTH but did not influence the rise in GH. The current studies suggest that the effects of L-arginine on the stimulation of GH and prolactin release are unlikely to be mediated via the generation of nitric oxide.

Adrenocorticotropic Hormone↗

PubMed1996

Insulin-like growth factor-I and- II in combination inhibit the release of growth hormone-releasing hormone from the rat hypothalamus in vitro.

This study was designed to investigate the feedback loop between insulin-like growth factor-I (IGF-I) and IGF-II and the hypothalamic hormones growth hormone-releasing hormone (GHRH) and somatostatin (SS) using an in vitro rat hypothalamic model. IGF-I and, to lesser extent, IGF-II, both activate type 1 IGF receptors, while type 2 receptors are activated by IGF-II alone. IGF-I, IGF-II, their various specific analogues (Des[1-3]IGF-I, [Arg54/Arg55]IGF-II and [Leu27]IGF-II), insulin and the type 2 receptor antagonist beta-galactosidase were used on their own or in combination to study their effect on GHRH and SS release. Our results suggest that the simultaneous activation of type 1 and type 2 IGF receptors is needed for the negative feedback effect of IGFs on GHRH release in this in vitro system, in agreement with earlier findings in vivo. Somatostatin was not altered by any combination of peptides.

Animals↗

PubMed1995

Benzodiazepines attenuate the pituitary-adrenal responses to corticotrophin-releasing hormone in healthy volunteers, but not in patients with Cushing's syndrome.

OBJECTIVE: The corticotrophin-releasing hormone (CRH) stimulation test has become established as a powerful tool in differentiating the source of ACTH in patients with Cushing's syndrome. Psychiatric symptoms are common in patients with Cushing's syndrome, and many patients with psychiatric illnesses may show disturbances of function of the pituitary-adrenal axis; both of these groups of patients may be receiving benzodiazepine drugs when presenting for evaluation of their possible endocrine problems. Both animal and human studies suggest that interactions occur between benzodiazepines and the hypothalamo-pituitary-adrenal axis. We have therefore evaluated the effects of a benzodiazepine drug on the pituitary-adrenal response to CRH. DESIGN: We have investigated the effects of 20 mg oral temazepam or placebo on serum cortisol and plasma ACTH after the administration of 100 micrograms i.v. human CRH in 12 healthy volunteers and in 9 patients with Cushing's syndrome. RESULTS: Temazepam significantly inhibited the peak serum/plasma levels and area under the curve for circulating cortisol and ACTH in normal subjects after CRH, but there was no such difference after temazepam in patients with Cushing's syndrome. CONCLUSIONS: Our results have shown that temazepam inhibits the pituitary-adrenal responses to human CRH in normal subjects, but not in those with Cushing's syndrome. We believe that inhibition of endogenous AVP by temazepam is the most likely explanation for our findings in healthy volunteers: the hypercortisolaemia in Cushing's syndrome suppresses the release of both endogenous CRH and AVP in portal blood which then results in abolition of the temazepam induced reduction in the pituitary-adrenal response to exogenous CRH, as seen in our patients. These effects of benzodiazepines should clearly be taken into account in patients using these compounds while undergoing endocrine assessment.

Adrenocorticotropic Hormone↗

PubMed1995

The effect of an opiate antagonist on the hormonal changes induced by hexarelin.

OBJECTIVE: Growth hormone-releasing peptides (GHRPs) stimulate growth hormone (GH) release in vitro and in vivo in animals and in humans. GHRPs were developed by modification of the structure of met-enkephalin but GHRP-6 does not activate opiod receptors in animal studies. These agents may well have diagnostic and/or long-term therapeutic potential in the future so their effects on opiod receptors need to be clarified in humans as well. Hexarelin is a recently developed six amino acid residue GHRP. DESIGN: We have investigated the effects of 100 micrograms/kg i.v. dose of the opiate antagonist naloxone and 2 micrograms/kg i.v. hexarelin or placebo on serum GH, prolactin, TSH, cortisol and plasma ACTH in 12 healthy volunteers in a double-blind, randomized trial. RESULTS: Hexarelin significantly stimulated the peak serum levels and area under the curve for circulating GH and this effect was not modulated by naloxone. Hexarelin also caused significant elevation of circulating prolactin, cortisol and ACTH but did not influence circulating TSH levels. The effect of naloxone on cortisol and ACTH was stimulatory, while it did not influence prolactin, GH and TSH levels. The effect of the two drugs together on cortisol and ACTH was less than additive. CONCLUSIONS: This study confirms that the activation of opiate receptors does not play a role in the GH-releasing effect of growth hormone-releasing peptides in humans.

Adrenocorticotropic Hormone↗

PubMedDate not supplied

Leptin in pituitary adenomas--a novel paracrine regulatory system.

A growing number of physiological and pathophysiological processes have been shown to be influenced by leptin apart from its first recognised role as a modulator of hypothalamic appetite and weight control centers. We investigated the presence and pattern of distribution of leptin mRNA and the mRNA of the long isoform of the leptin receptor in the normal pituitary and in different types of pituitary adenomas. We also studied leptin secretion from human pituitary tumors in culture, and the in vitro pituitary hormone release following stimulation with human leptin. Leptin mRNA expression was detected at a low level of expression in 50% of tumors but in none of the normal pituitaries. By immunohistochemistry, leptin was present in occasional scattered cells in the normal pituitary and in pituitary tumors. The leptin receptor long isoform was detected in the majority (65%) of pituitary tumors and in all normal pituitaries. It did not segregate with any particular tumor type, and varying levels of expression were detected between the tissues studied. 34% of pituitary adenomas showed leptin release into the incubation media during in vitro culture. Leptin mRNA, the mRNA of the long isoform of the receptor, or in vitro leptin release, did not correlate with tumor type or with any of the other pituitary hormones released. In vitro leptin stimulation of pituitary tumors caused stimulation of FSH and a-subunit secretion from a non-functioning adenoma and TSH secretion from a somatotroph adenoma. As the co-localisation of ACTH and leptin in corticotroph cells was previously suggested, we investigated whether in vivo ACTH release is accompanied by a simultaneous plasma leptin level rise (i) in peripheral plasma samples after food intake-induced ACTH rise in healthy obese and nonobese individuals and (ii) in petrosal sinus samples after CRH injection in Cushing's disease patients. Our data suggest that a rise in ACTH levels is not accompanied by detectable rise in leptin levels in peripheral and in petrosal sinus blood samples. In summary, leptin is synthesized and stored within the pituitary and may modulate other pituitary hormone secretion, although probably it does not contribute to plasma leptin level changes. Pituitary leptin may therefore be a novel paracrine regulator of pituitary function.

Adenoma↗

PubMedDate not supplied

Leptin and puberty: a review.

Over the last few years, many studies have focused on leptin, the product of the LEP (ob) gene, searching for a possible link between energy balance and reproduction. The involvement of this peptide in the regulation of the hypothalamo-pituitary-adrenal, gonadal, thyroid and somatotroph axes suggests that leptin might play a pivotal role in coordinating the activity of these axes and their relationship with the body's energy balance. The effects of leptin on hypothalamic, pituitary and peripheral hormone levels, as well as the presence of the leptin receptor in a variety of tissues, suggest both an endocrine and a paracrine mode of action. Particular attention was paid to the effect of leptin on the gonadal axis as infertility, a characteristic feature of both the leptin deficient ob/ob mice and the leptin receptor mutant db/db mice, could be corrected in ob/ob mice by leptin administration. Considerable leptin level changes were observed during puberty both in animal and human studies. A matter of controversy is the precise role of leptin in the onset of puberty: is leptin the signal that initiates puberty and the accompanying hormonal changes, or has leptin only a permissive but key role for the onset of puberty, as likely seems to be the case for the maintenance of a functional gonadotroph axis? On current evidence, a mainly permissive role seems most probable.

Animals↗