Biomedical subjects

Willis K Samson

Publications and source records attributed to Willis K Samson.

26 records · Page 2Linked to original sources

PubMed2003

Hypothalamic localization of steroidogenic acute regulatory protein: the missing piece of the puzzle is found.

Substantial evidence has accumulated for the existence in brain of steroid synthetic mechanisms similar to, but independent from those present in peripheral tissues. Recent findings suggest that many of the enzymes necessary for steroidogenesis occur in brain neurons and glia, and now a broader distribution of that enzymatic machinery has been identified, providing evidence for local, paracrine actions of brain-derived steroids in the neuroendocrine hypothalamus.

Animals↗

PubMed2003

The other side of the orexins: endocrine and metabolic actions.

Although it is clear that the orexin/hypocretin peptides have a significant, physiologically relevant role in sleep/wakefulness, a broader picture has emerged indicating metabolic actions that may depend upon both neural and endocrine mechanisms for their manifestation. The ability of exogenous peptide to activate sympathetic tone, increase locomotor activity, and alter feeding behavior, together with the observed alterations in those functions in knockout animals, strongly suggests important neural actions of the endogenous orexins/hypocretins. Likewise, the action of exogenously administered peptides to alter endocrine function, in particular corticotropin release, has now been mirrored by potential endocrinopathies in knockout animals. Thus these pluripotent peptides hold great potential not only for the treatment of human narcolepsy but also to provide insight into the coordinated regulation of multiple physiological systems.

Animals↗

PubMed2003

Neuropeptide W acts in brain to control prolactin, corticosterone, and growth hormone release.

The endogenous, peptide ligand for the orphan receptors GPR7 and GPR8 was identified to be neuropeptide W (NPW). Because these receptors are expressed in brain and in particular in hypothalamus, we hypothesized that NPW might interact with neuroendocrine systems that control hormone release from the anterior pituitary gland. No significant effects of NPW were observed on the in vitro releases of prolactin (PRL), ACTH, or GH when log molar concentrations ranging from 1 pM to 100 nM NPW were incubated with dispersed anterior pituitary cells. However, NPW, when injected into the lateral cerebroventricle of conscious, unrestrained male rats, in a dose-related fashion elevated PRL and corticosterone and lowered GH levels in circulation. The threshold dose for all three effects was 1.0 nmol. We conclude that endogenous NPW may play a regulatory role in the organization of neuroendocrine signals accessing the anterior pituitary gland but does not itself act as a true releasing or inhibiting factor in the gland. Central administration of NPW23 also stimulated water drinking and food intake. The ability of exogenous peptide to decrease GH but stimulate PRL secretion and activate the hypothalamo-pituitary adrenal axis, together with the observed behavioral effects, suggests that endogenous NPW may play a role in the hypothalamic response to stress.

Adrenocorticotropic Hormone↗

PubMed2002

Adrenomedullin and the integrative physiology of fluid and electrolyte balance.

Adrenomedullin (AM) is hypothesized to be a physiologically relevant regulator in fluid and electrolyte homeostasis. AM acts within the central nervous system to inhibit both water and salt intake. The peptide has direct actions in the hypothalamus to decrease vasopressin secretion and in the pituitary gland to inhibit ACTH release. AM decreases production and release of aldosterone from the adrenal glands and acts directly in the kidneys to increase renal blood flow and cause diuresis and natriuresis. Whether or not these complementary actions in brain, pituitary, adrenal gland, and kidney reflect coordinated regulatory mechanisms is currently unknown. Development of molecular tools to determine the physiologic role of endogenous AM will greatly enhance our understanding of AM and its regulation of fluid and electrolyte homeostasis.

Adrenal Glands↗

PubMed2002

Orexin actions in hypothalamic paraventricular nucleus: physiological consequences and cellular correlates.

Orexinergic neurons originating in the perifornical, lateral hypothalamus project to numerous brain sites including neuroendocrine centers known to be important in the physiologic response to stress. Those projections suggest an action of endogenous orexin on adrenocorticotropin (ACTH) release, either by neuromodulatory effects in the paraventricular nucleus (PVN), or by neuroendocrine actions in the pituitary gland following release into the median eminence. We sought to determine if exogenously applied orexin A might act in the brain to alter ACTH release and to determine if a site of action in the hypothalamic paraventricular nucleus could be identified. Cerebroventricular administration of orexin A in conscious male rats resulted in a dose-related elevation in circulating ACTH levels. At 30 min post-infusion, ACTH levels were elevated 2.5-fold by the low dose of orexin A (0.3 nmol), 5.7-fold by the middle dose tested (1.0 nmol), and 7.5-fold by the highest dose tested (3.0 nmol). Pretreatment with a CRH-antagonist (i.v.) blocked the ability of i.c.v. administered orexin A to activate the hypothalamo-pituitary-adrenal (HPA) axis. Bath application of orexin A in hypothalamic slice preparations resulted in depolarizations (8.0+/-0.6 mV), accompanied by increases in spike frequency in identified magno- and parvocellular neurons in the PVN. Our data suggest a potential role for endogenous orexin in the hypothalamic regulation of stress hormone secretion.

Adrenocorticotropic Hormone↗

PubMed2002

Ribozyme compromise of adrenomedullin mRNA reveals a physiological role in the regulation of water intake.

The adrenomedullin (AM) preprohormone is posttranslationally processed to result in two biologically active fragments, AM and proadrenomedullin NH(2)-terminal 20 peptide (PAMP). AM is thought to play a role in fluid and electrolyte balance by acting in brain to inhibit salt and water appetite and in the kidney to cause diuresis and natriuresis. We previously have shown that AM is necessary for the short-term regulation of salt intake. In this paper, we have designed a ribozyme, a catalytic RNA molecule, which specifically recognizes and cleaves the AM transcript. In cultured vascular smooth muscle cells, ribozyme treatment lowered AM mRNA and reduced peptide content. Intracerebroventricular administration of the ribozyme lowered hypothalamic AM content and led to an exaggerated drinking response in rats, demonstrating that endogenous, brain-derived AM is physiologically relevant and necessary for short-term control of water intake.

Adrenomedullin↗

PubMedDate not supplied

Knockout knockouts.

Deletion of the genes for a variety of neuropeptides or their receptors has provided great insight into the physiological roles played by those peptides. Strikingly, several of these knockout models mature into very similar metabolic phenotypes, providing clues to the mechanisms underlying the regulation of glucose homeostasis, cardiovascular regulation and the hormonal response to stress.

Animals↗

PubMedDate not supplied

Prolactin-releasing peptide and its homolog RFRP-1 act in hypothalamus but not in anterior pituitary gland to stimulate stress hormone secretion.

The RF-amide peptides (RFRPs), including prolactin (PRL)-releasing peptide-31 (PrRP-31) and RFRP-1, have been reported to stimulate stress hormone secretion by either direct pituitary or indirect hypothalamic actions. We examined the possible direct effects of these peptides on PRL and adrenocorticotropin (adrenocorticotropic hormone [ACTH]) release from dispersed anterior pituitary cells in culture and on PRL and ACTH secretion following intracerebroventricular (i.c.v.) administration in vivo. Neither peptide significantly altered PRL or ACTH release from cultured pituitary cells (male rat donors). Central administration of 1.0 and 3.0 nmol of PrRP-31, but only the higher dose of RFRP-1, significantly elevated serum corticosterone levels in conscious male rats. The effect of PrRP-31 was not blocked by pretreatment (i.v.) with the corticotropin-releasing hormone (CRH) antagonist, alpha-helical CRH 9-41; however, pretreatment of the animals (i.v.) with an antiserum to CRH significantly lowered the hypothalamic-pituitary- adrenal axis response to central administration of PrRP-31. On the other hand, the release of PRL was significantly elevated by 3.0 nmol of RFRP-1, but not PrRP-31, in similarly treated, conscious male rats. Pretreatment with the catecholamine synthesis inhibitor, alpha-methyl-para-tyrosine, prevented the stimulation of PRL secretion observed following central administration of RFRP-1. RFRP-1 similarly did not alter PRL secretion in rats pretreated with the dopamine, D(2) receptor blocker, domperidone. These results suggest that the RF-amide peptides are not true neuroendocrine regulators of stress hormone secretion in the rat but, instead, act centrally to alter the release of neuroendocrine factors that do act in the pituitary gland to control PRL and ACTH release. In the case of RFRP-1, stimulation of PRL secretion is potentially owing to an action of the peptide to inhibit dopamine release into the median eminence. The corticosterone secretion observed following central administration of PrRP-31 does not appear, based on our current results, to be solely owing to an action of the peptide on CRH-producing neurons but, instead, may be a result of the ability of PrRP-31 to increase as well the exposure of the corticotrophs in vivo to other ACTH secretagogues, such as oxytocin or vasopressin.

Adrenocorticotropic Hormone↗