The secretion of glucocorticoids (GCs) is a classic endocrine response to stress. Despite that, it remains controversial as to what purpose GCs serve at such times. One view, stretching back to the time of Hans Selye, posits that GCs help mediate the ongoing or pending stress response, either via basal levels of GCs permitting other facets of the stress response to emerge efficaciously, and/or by stress levels of GCs actively stimulating the stress response. In contrast, a revisionist viewpoint posits that GCs suppress the stress response, preventing it from being pathologically overactivated. In this review, we consider recent findings regarding GC action and, based on them, generate criteria for determining whether a particular GC action permits, stimulates, or suppresses an ongoing stressresponse or, as an additional category, is preparative for a subsequent stressor. We apply these GC actions to the realms of cardiovascular function, fluid volume and hemorrhage, immunity and inflammation, metabolism, neurobiology, and reproductive physiology. We find that GC actions fall into markedly different categories, depending on the physiological endpoint in question, with evidence for mediating effects in some cases, and suppressive or preparative in others. We then attempt to assimilate these heterogeneous GC actions into a physiological whole. (Endocrine Reviews 21: 55‐ 89, 2000)

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How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions.

The secretion of growth hormone (GH) is regulated through a complex neuroendocrine control system, especially by the functional interplay of two hypothalamic hypophysiotropic hormones, GH-releasing hormone (GHRH) and somatostatin (SS), exerting stimulatory and inhibitory influences, respectively, on the somatotrope. The two hypothalamic neurohormones are subject to modulation by a host of neurotransmitters, especially the noradrenergic and cholinergic ones and other hypothalamic neuropeptides, and are the final mediators of metabolic, endocrine, neural, and immune influences for the secretion of GH. Since the identification of the GHRH peptide, recombinant DNA procedures have been used to characterize the corresponding cDNA and to clone GHRH receptor isoforms in rodent and human pituitaries. Parallel to research into the effects of SS and its analogs on endocrine and exocrine secretions, investigations into their mechanism of action have led to the discovery of five separate SS receptor genes encoding a f...

Neuroendocrine Control of Growth Hormone Secretion

Opioid abuse has increased in the last decade, primarily as a result of increased access to prescription opioids. Physicians are also increasingly administering opioid analgesics for noncancer chronic pain. Thus, knowledge of the long-term consequences of opioid use/abuse has important implications for fully evaluating the clinical usefulness of opioid medications. Many studies have examined the effect of opioids on the endocrine system; however, a systematic review of the endocrine actions of opioids in both humans and animals has, to our knowledge, not been published since 1984. Thus, we reviewed the literature on the effect of opioids on the endocrine system. We included both acute and chronic effects of opioids, with the majority of the studies done on the acute effects although chronic effects are more physiologically relevant. In humans and laboratory animals, opioids generally increase GH and prolactin and decrease LH, testosterone, estradiol, and oxytocin. In humans, opioids increase TSH, whereas in rodents, TSH is decreased. In both rodents and humans, the reports of effects of opioids on arginine vasopressin and ACTH are conflicting. Opioids act preferentially at different receptor sites leading to stimulatory or inhibitory effects on hormone release. Increasing opioid abuse primarily leads to hypogonadism but may also affect the secretion of other pituitary hormones. The potential consequences of hypogonadism include decreased libido and erectile dysfunction in men, oligomenorrhea or amenorrhea in women, and bone loss or infertility in both sexes. Opioids may increase or decrease food intake, depending on the type of opioid and the duration of action. Additionally, opioids may act through the sympathetic nervous system to cause hyperglycemia and impaired insulin secretion. In this review, recent information regarding endocrine disorders among opioid abusers is presented.

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The Effects of Opioids and Opioid Analogs on Animal and Human Endocrine Systems

The neuroanatomy, neurophysiology, and neurochemistry of pain, stress, and analgesia in newborns and children.

Studies of prehistoric patterns of health and disease focus on interpretations of the evidence from hard tissue remains of past peoples. These interpretations are based on observations of living peoples and the sources of stress which may be expected to leave a record in their bones and teeth. One presumed source of stress that has received wide attention in the recent literature is weaning. The process of weaning is often associated with elevated risks of infant mortality and morbidity because infants no longer receive passive immunity from their mothers, and they are exposed to new sources of infection through the weaning diet. The process of weaning has also been tied to the duration of the contraceptive effects of nursing and the return of fecundity, which in turn provides information about birth spacing and population growth. Recently some of the basic assumptions about nursing and weaning, and their effects on morbidity, mortality and population growth, have been challenged, based on new technical and cross-cultural information. It is clear from the demographic literature that some studies based on skeletal samples tend to be too simplistic in terms of the causes of infant morbidity and mortality. This paper reviews current research which relates weaning and infant mortality to health and reproduction in past populations and evaluates studies of enamel hypoplasia and bone chemistry for reconstructing infant feeding practices in the past. © 1996 Wiley-Liss, Inc.

Weaning and infant mortality: Evaluating the skeletal evidence

Hormonal and metabolic responses to an enkephalin analogue in normal man

Opiate peptides are known to influence the secretion of several anterior pituitary hormones under basal conditions. Further studies on prolactin, GH and TSH have therefore been performed in normal subjects, under basal and stimulated conditions, using an opiate agonist and antagonist. Sixteen mg naloxone had no effect on the basal release of prolactin or GH, but lowered TSH. An infusion of the met-enkephalin analogue DAMME (1 mg) increased GH, and produced an exaggerated response of both prolactin and TSH to 200 micrograms TRH i.v. The peak responses of both prolactin and GH to hypoglycaemia were unaffected by pretreatment with either low-dose (0.4 mg) or high-dose (25 mg) naloxone, or DAMME (0.25 mg). These results suggest that opiate peptides are unlikely to play a major role in the tonic or hypoglycaemia-stimulated release of prolactin and GH, although they may be of importance in the control of TSH.

Studies of the opiate control of prolactin, gh and tsh

Management of the pregnant diabetic: home or hospital, with or without glucose meters?

SUMMARY
The effects of single oral doses of 0.2 mg of lisuride hydrogen maleate, a semisynthetic ergot derivative, on serum levels of prolactin (PRL), growth hormone (GH), thyroid stimulating hormone (TSH), luteinizing hormone (LH), follicle stimulating hormone (FSH), cortisol and blood glucose were studied in six normal males. Lisuride effectively inhibited basal PRL secretion as well as the PRL response to TRH given 3 h later. In addition, the drug raised basal GH levels and decreased basal and TRH stimulated TSH secretion. No significant differences between lisuride and control were observed in basal LH and FSH, LHRH stimulated gonadotrophins or in cortisol. Drowsiness was noted by all subjects, one became nauseated and another vomited, 60 and 90 min respectively after administration of lisuride. No changes were seen in pulse rate and blood pressure. The endocrine effects of lisuride were attenuated by the prior administration of the dopamine antagonist metoclo-pramide. These results suggest that lisuride acts as a long-acting dopamine agonist and that therefore this drug could be of therapeutic use in hyperprolactinaemic states and acromegaly.

The effect of lisuride hydrogen maleate, an ergot derivative on anterior pituitary hormone secretion in man.

SUMMARY
Serial blood sampling in nine patients treated with cimetidine (1 g/day) showed that PRL values were within the normal range apart from a stress-induced initial rise. Hormonal and metabolic profiles from 08.30 to 18.30 h were performed in six patients before and after 1 month's treatment with cimetidine (1 g/day). Circulating PRL, LH, FSH, GH, TSH T3, T4 and testosterone were similar before and after treatment. The mean blood glucose fell from 5·4 ± 0·3 mmol/l to 4·8 ± 0·2 mmol/l on cimetidine (P<0·02). Small changes were also observed in blood pyruvate, lactate, 3-hydroxybutyrate and the (lactate)/(pyruvate) ratio. The effects of oral or i.v. cimetidine on the circulating concentrations of insulin, glucose and intermediary metabolites were investigated in normal subjects. Intravenous cimetidine (100 mg/h for 4 h) given to fasting subjects decreased blood glucose and serum insulin by 15 and 34% respectively at 150 min. During an oral GTT, i.v. cimetidine caused a striking decline in blood glucose, lactate and pyruvate responses compared with control studies, although the serum insulin was similar to control values. When given for 48 h before the study, oral cimetidine did not alter basal serum insulin and blood glucose, lactate, pyruvate, alanine, glycerol and 3-hydroxybutyrate levels. However, 150 min after an oral GTT the serum insulin was increased by 47% by oral cimetidine although the blood glucose was not significantly changed compared with the control day. Oral cimetidine had no effect on the blood glucose or serum insulin during an i.v. GTT. These results show that oral cimetidine given at therapeutic doses to patients with peptic ulcers does not produce consistent changes in circulating anterior pituitary hormones. Oral cimetidine given to patients for 1 month and i.v. cimetidine given to normal subjects have mild hypoglycaemic effects. Oral cimetidine administered over 48 h to normal subjects has little effect on blood glucose concentration.

W. A. Stubbs

Papers

Hormonal and metabolic responses to an enkephalin analogue in normal man

Studies of the opiate control of prolactin, gh and tsh

Management of the pregnant diabetic: home or hospital, with or without glucose meters?

The effect of lisuride hydrogen maleate, an ergot derivative on anterior pituitary hormone secretion in man.

The endocrine and metabolic effects of cimetidine