Search Results
You are looking at 1 - 5 of 5 items for
- Author: S. Tsagarakis x
- Refine by access: All content x
Search for other papers by A. Grossman in
Google Scholar
PubMed
Search for other papers by S. Tsagarakis in
Google Scholar
PubMed
In the halcyon days when life was simple, many thought that pituitary hormones were under the control of single hypothalamic factors which regulated their synthesis and release. Matters became a little more complex when the search for growth hormone (GH)-releasing hormone was punctuated by the discoveries of somatostatin, which inhibited both GH and thyrotrophin (TSH), by the co-release of TSH and prolactin by thyrotrophin-releasing hormone, and then by the substantiation of other prolactin-releasing factors such as vasoactive intestinal peptide. It has since become increasingly clear that pituitary peptides are regulated by a whole series of hypothalamic factors, both stimulatory and inhibitory, and are also subject to intrapituitary paracrine modulation.
There has, however, been slow acceptance of the concept that the release of adrenocorticotrophin (ACTH) too may be finely tuned by an inhibitory factor. There is clearly a predominant role for a stimulatory factor to ACTH release, the earliest candidate for
Search for other papers by J. Ibanez-Santos in
Google Scholar
PubMed
Search for other papers by S. Tsagarakis in
Google Scholar
PubMed
Search for other papers by L. H. Rees in
Google Scholar
PubMed
Search for other papers by G. M. Besser in
Google Scholar
PubMed
Search for other papers by A. Grossman in
Google Scholar
PubMed
ABSTRACT
Atrial natriuretic peptide, ANP(99–126), is derived from cardiac atrial tissue and has potent effects on salt and water homeostasis, including the inhibition of aldosterone and vasopressin release. Recent studies have also suggested that it may suppress the pituitary-adrenal axis. In addition, N-truncated forms of ANP, such as ANP(103–126), have been identified within the central nervous system, with a prominent hypothalamic localization in the paraventricular nucleus. We have therefore investigated whether ANP(99–126) and ANP(103–126) are able to modulate the release of the principal ACTH-releasing factor, corticotrophin-releasing factor-41 (CRF-41), from the rat hypothalamus in vitro.
The static incubation system has been previously described in detail. Male Wistar rats were decapitated between 09.00 and 09.30 h, their hypothalami rapidly removed, and four half-hypothalami incubated for 20-min intervals following a period of stabilization. The effect of the ANP peptides on the basal (B) and KCl (28 mmol/l)-stimulated (S) release of immuno-reactive CRF-41 was studied by means of successive incubations in the absence (B1, SI) and presence (B2, S2) of the peptides. The ratios B2: B1 and S2: S1 were compared with parallel control incubations by ANOVA.
Neither form of ANP had any effect on the basal release of CRF-41. ANP(99–126) caused a dose-dependent inhibition of CRF-41 release in the concentration range 1–100 nmol (P < 0·01). ANP(103–126) also suppressed the release of CRF-41 in the concentration range 100 pmol/l–100 nmol/l (P < 0·01), with a minimum S2:S1 ratio at 10 nmol/l, and a decrease in effect at 100 nmol/l. Finally, the stimulation of CRF-41 release induced by noradrenaline (10 nmol/l and 1 μmol/l) was non-competitively antagonized by 100 nmol ANP(99–126)/l and 10 nmol ANP(103–126)/l.
It was concluded that ANP may be an important regulator of the pituitary-adrenal axis by interaction with CRF-41. As there are data indicating that ANP may also directly inhibit the pituitary corticotroph, it would appear that central ANP is intimately involved in pituitary-adrenal function.
Journal of Endocrinology (1990) 126, 223–228
Search for other papers by E. Ur in
Google Scholar
PubMed
Search for other papers by M. Faria in
Google Scholar
PubMed
Search for other papers by S. Tsagarakis in
Google Scholar
PubMed
Search for other papers by J. V. Anderson in
Google Scholar
PubMed
Search for other papers by G. M. Besser in
Google Scholar
PubMed
Search for other papers by A. Grossman in
Google Scholar
PubMed
ABSTRACT
Whilst it has been postulated that atrial natriuretic peptide (ANP) may modulate pituitary hormone release, several investigations in non-human species have reported conflicting results when looking for an effect on the hypothalamo-pituitary-adrenal axis. However, in a recent study significant inhibition of corticotrophin-releasing hormone (CRH)-stimulated ACTH in cultured rat anterior pituitary cells occurred only with the complete peptide α-ANP(1–28).
We have therefore investigated whether this form of ANP can inhibit CRH-stimulated ACTH and cortisol release in human subjects. Six healthy male volunteers received human α-ANP or placebo, and human CRH or placebo, on four separate occasions.
ANP was infused at a rate of 0·01 μg/kg per min in order to achieve levels in the high physiological range. CRH was given as a bolus dose of 100 μg 30 min into the ANP infusion. Cortisol and ANP were measured by radioimmunoassay, the latter after extraction. ACTH was measured by immunoradiometric assay. The data were analysed by Student's paired t-test on basal, peak and incremental levels. Basal levels of ANP were within the normal range (2–5 pmol/l). With ANP infusion, mean ± s.e.m. peak ANP levels were 29·6±3·1 pmol/l. There were no significant differences in mean basal cortisol and ACTH levels on each of the 4 study days. Mean peak cortisol and ACTH levels after CRH and ANP did not significantly differ from those achieved with CRH and placebo ANP. We thus conclude that at high physiological doses, circulating ANP does not inhibit CRH-stimulated ACTH or cortisol release.
Journal of Endocrinology (1991) 131, 163–167
Search for other papers by F. Ge in
Google Scholar
PubMed
Search for other papers by S. Tsagarakis in
Google Scholar
PubMed
Search for other papers by L. H. Rees in
Google Scholar
PubMed
Search for other papers by G. M. Besser in
Google Scholar
PubMed
Search for other papers by A. Grossman in
Google Scholar
PubMed
ABSTRACT
Secretion of GH in the rat has been shown to be dependent upon age and sex. Using rat hypothalamic explants in vitro, we have studied the release and hypothalamic content of GH-releasing hormone (GHRH) and somatostatin in male and female Wistar rats at four different ages (10, 30 and 75 days, and 14 months). Basal release of GHRH was not significantly different between male and female rats, but at all ages males released more GHRH in response to stimulation by both 28 and 56 mmol potassium/l than female rats (P<0·05). Neither basal nor potassium-stimulated release of GHRH altered with age. In contrast, both basal and potassium-stimulated secretion of somatostatin increased significantly (P<0·01) with age, but was the same in the two sexes. Hypothalamic GHRH content, as assessed by the extractable tissue content following incubation, was significantly (P<0·01) lower in 10-day-old rats compared with older rats, but remained constant after 30 days of age. Somatostatin content, in contrast, increased progressively with age (P<0·01). The hypothalamic content of the two peptides was the same in both sexes.
In conclusion, our findings demonstrate that male rats release more GHRH in vitro than female rats, possibly reflecting the increased pulse amplitude of GH seen in males in vivo; the progressive fall in secretion of GH previously reported during ageing appears to parallel the progressive increase in somatostatin release and content seen in our in-vitro system.
Journal of Endocrinology (1989) 123, 53–58
Search for other papers by P. Navarra in
Google Scholar
PubMed
Search for other papers by S. Tsagarakis in
Google Scholar
PubMed
Search for other papers by D. H. Coy in
Google Scholar
PubMed
Search for other papers by L.H. Rees in
Google Scholar
PubMed
Search for other papers by G. M. Besser in
Google Scholar
PubMed
Search for other papers by A. B. Grossman in
Google Scholar
PubMed
ABSTRACT
It has been suggested that melanin concentrating hormone (MCH) possesses potent corticotrophin (ACTH) inhibitory activity, on the basis of the inhibitory effects displayed by salmon MCH on ACTH release from either trout or rat isolated pituitary fragments. Recently, rat MCH has been characterised, and this prompted us to investigate the putative inhibitory activity of synthetic rat MCH on basal and stimulated ACTH secretion from freshly-dispersed rat pituitary cells or incubated rat pituitary fragments, as well on KCl (28 mmol/l) or noradrenaline-evoked release of corticotrophin releasing hormone-41 (CRH-41) from rat hypothalamic explants in vitro. There were no effects of rat MCH on either CRH-41 or ACTH release in vitro.
