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Biomedical subjects

L H Rees

Publications and source records attributed to L H Rees.

At least 181 records · Page 10Linked to original sources
PubMed1982

Opiate modulation of the pituitary-adrenal axis: effects of stress and circadian rhythm.

The opiate control of the pituitary-adrenal axis has been investigated in normal subjects. The infusion of 1 mg of the met-enkephalin analogue, DAMME, led to a fall in circulating cortisol in spite of a fall in blood pressure. Conversley, 16 mg of the opiate antagonist, naloxone led to brisk and pronounced elevations in plasma ACTH, lipotrophin (LPH) and cortisol. The rise above basal levels was consistent, irrespective of whether the infusion was given at 09.00, 18.00, or 23.00 h; the peak response obtained was significantly less at 23.00 h than at either 09.00 or 18.00 h. Finally, insulin-induced hypoglycaemia (0.15 u/kg) or naloxone (25 mg) produced a similar rise in plasma cortisol which was no different when the two stimuli were combined. It is suggested that there is a constant tonic inhibition of the pituitary-adrenal axis by endogenous opiates throughout 24 h, and that the circadian rhythm of ACTH/LPH secretion is not due to changes in opiate tone. However, disinhibition of this tone is likely to be responsible, at least in part, for the rise in cortisol in response to hypoglycaemic stress.

Adolescent↗
PubMed1982

Opiate mediation of amenorrhoea in hyperprolactinaemia and in weight-loss related amenorrhoea.

Endogenous opiates are involved in the control of pituitary gonadotrophin and PRL secretion, and possibly of food intake. Both hyperprolactinaemia and weight loss (especially in anorexia nervosa) are frequently associated with amenorrhoea and an absence of gonadotrophin pulsatility. Since it has been suggested that increased endogenous opiate tone may operate in both conditions, we infused high-doses of naloxone into twelve patients with amenorrhoea of whom five had hyperprolactinaemia and seven had weight-loss related amenorrhoea. Eleven of the twelve patients had low levels of oestradiol (less than 50 pmol/l). Naloxone induced a marked rise in both LH and FSH levels in all of the five hyperprolactinaemic patients. In contrast, the patients with weight-loss amenorrhoea responded to naloxone with only a small or no rise in gonadotrophins. There was no consistent change in PRL in either group of patients. It is concluded that in hyperprolactinaemia, but not weight-loss amenorrhoea, there is an important endogenous opiate-mediated tonic inhibition of secretion of hypothalamic gonadotrophin releasing hormone.

Adolescent↗
PubMed1982

hCG beta producing pineal choriocarcinoma.

A patient is described with tumours in the region of the pineal gland and anterior hypothalamus associated with high levels of hCG beta in the serum and cerebrospinal fluid (CSF). He presented aged 19, with hypopituitarism, but persistent secondary sexual characteristics. LH immunoreactivity in serum was due to the hCG beta which probably caused the elevated level of testosterone. Following cranial irradiation the tumour became undetectable and hCG beta was eradicated from the serum and CSF. The patient later died because of an intramedullary metastasis of choriocarcinoma in the cervical spinal cord. The endocrine details of six previously reported intracranial neoplasms which have been shown to secrete hCG beta are reviewed. Only two of these involved the pineal region. Chorionic gonadotrophin production by this tumour enabled early detection of its recurrence. It is unclear how often precocious puberty is caused by tumours producing hCG beta, but patients presenting either with that problem or a pineal tumour should have circulating hCG beta measured.

Adult↗
PubMed1982

Pulsatile gonadotrophin secretion in hyperprolactinaemic amenorrhoea an the response to bromocriptine therapy.

Serum gonadotrophin concentrations were measured every 15 min for 8 h in six patients before and at weekly intervals during initiation of bromocriptine treatment of hyperprolactinaemic amenorrhoea. Before treatment mean gonadotrophin levels were similar to those found in the normal follicular phase, but LH secretion was characterized by infrequent pulses of large amplitude. In three subjects the patterns of LH pulsatility and serum oestradiol levels returned to normal within 7 days of starting bromocriptine. The other three subjects responded with an increase in the frequency of LH pulses and mean LH levels, but little rise in oestradiol. Thus some hyperprolactinaemic subjects have a defect in the ovarian response to endogenous gonadotrophin stimulation, which may persist for a few weeks after return of prolactin levels to normal. The restoration of a normal rate of LH pulsatility with bromocriptine can occur without any change in serum oestradiol concentration.

Adult↗
PubMed1982

Male gonadal function in coeliac disease: 1. Sexual dysfunction, infertility, and semen quality.

The prevalence of hypogonadism, sexual dysfunction and abnormalities of semen quality was determined in 28 consecutive males with coeliac disease. These observations were related to jejunal morphology and nutritional status, and were compared with findings in 19 men with Crohn's disease of similar age and nutritional status. Two of the 28 coeliacs (7%) had clinical evidence of hypogonadism but impotence and decreased sexual activity occurred more commonly, the latter apparently improving after gluten withdrawal. Of the married coeliacs, 19% had infertile marriages, a value greater than expected in the general population. Hypogonadism and sexual dysfunction were not detected in our patients with Crohn's disease. Seminal analysis in coeliacs revealed marked abnormalities of sperm morphology and motility, but only the former appeared to improve after gluten withdrawal. Similar abnormalities, however, were also detected in patients with Crohn's disease, although, unlike the coeliacs, 46% also had reduced concentrations of spermatozoa. Semen quality in coeliac disease could not be clearly related to general or specific (serum vitamin B(12) and red cell folate) nutritional deficiencies or to fertility, although sperm motility was markedly reduced in two of the three coeliacs with infertile marriages. The presence of antisperm antibodies did not appear to be an important aetiological factor in male infertility in coeliac disease. The pathogenesis of infertility and sexual dysfunction in coeliac disease remains unclear, suggesting that factors such as endocrine dysfunction or other specific nutritional deficiency may be involved.

Adolescent↗
PubMed1982

Stability of pro-opiocortin-related peptides in post-mortem mouse brain tissue.

The stability of pro-opiocortin-related peptides, growth hormone and somatostatin was investigated in mouse brain for up to 72 h post mortem. The peptide content in acid extracts of whole mouse brain was measured by radioimmunoassay and the molecular forms characterised by chromatography on Sephadex G-50 under acid-dissociating conditions. The brain content of the pro-opiocortin-related peptides and growth hormone rose markedly with time after death and chromatography showed this to be due to an increase in the same molecular forms present immediately post mortem, with no significant peptide fragmentation or precursor cleavage. These rises were not seen in the brains of those animals hypophysectomized at death. In contrast, the levels of somatostatin were not significantly altered post mortem though there was a shift in the relative distribution of immunoactivity between the different molecular forms. These results indicate that the peptide content of post-mortem mouse brain may be affected by leakage of pituitary contents and that even though the levels of other neuropeptides may not change, their molecular forms may be altered.

Adrenocorticotropic Hormone↗
PubMed1982

Long term improvement in insulin response with gliclazide treatment.

Blood glucose, plasma insulin and C-peptide concentrations were measured in response to a standard meal in eight Type 2 (non-insulin dependent) diabetic patients before and after treatment with gliclazide for 33 +/- 9 months. Compared with the pre-treatment values, blood glucose levels remained significantly lower (p less than 0.00001), while plasma insulin and C-peptide concentrations remained significantly higher (p less than 0.00001 and p less than 0.001 respectively) throughout the treatment period. In contrast to previous studies, these findings demonstrate that prolonged sulphonylurea treatment produces continued enhancement of B cell secretion.

Adult↗
PubMed1981

Chlorpropamide alcohol flush and circulating met-enkephalin: a positive link.

Chlorpropamide-alcohol flushing may be due to sensitivity to endogenous opiates. To investigate this possibility the plasma met-enkephalin and beta-endorphin responses to sherry with and without chlorpropamide were studied in six patients with non-insulin dependent diabetes and in six normal subjects. After chlorpropamide all patients showed a rise in met-enkephalin concentrations from a basal level of 50 +/- 7.2 ng/l to a peak of 75 +/- 8.1 ng/l (p less than 0.001). In contrast, before chlorpropamide treatment was started met-enkephalin values did not change after alcohol. No significant changes in beta-endorphin values were observed. In six normal subjects pretreated with chlorpropamide the met-enkephalin concentration also rose from a basal level of 72 +/- 15 ng/l to a peak of 103 +/- 9.4 ng/l (p less than 0.002). Again, the met-enkephalin rise was not observed after placebo. Neither beta-endorphin concentrations nor facial temperature changed significantly. These data suggest that endogenous opiates may be implicated in CPAF. Furthermore, this is the first study in which a significant change in circulating met-enkephalin values has occurred.

Chlorpropamide↗
PubMed1981

A study of 24-hour profiles of plasma met-enkephalin in man.

Met-enkephalin has recently been demonstrated to circulate in human plasma and using this highly specific extracted radioimmunoassay the fluctuations of plasma Met-enkephalin in man were studied over 24 h. The subjects were 6 healthy volunteers. Following a 24 h adaptation period in the metabolic ward and sleep laboratory, an i.v. catheter was inserted. Blood samples were taken at hourly intervals through the day and at 30 min intervals between 23.00 h and 07.00 h. Sleep was monitored polygraphically. There was no regular rhythm discernible in plasma Met-enkephalin levels throughout the 24 h, nor was there any relationship with sleep or food intake. In a further 3 subjects beta-LPH and beta-endorphin levels as estimated by N- and C-terminal beta-LPH radioimmunoassay were elevated on waking compared with 01.00 h, suggesting a nyctohemeral rhythm. In contrast to the correlated circadian fluctuations in beta-LPH, ACTH and beta-endorphin levels therefore, the lack of circadian rhythmicity and dissociation of plasma Met-enkephalin from plasma levels of the former group of peptides suggests control mechanisms for the secretion of Met-enkephalin are quite different and adds support to the concept of separate Met-enkephalin precursors.

Adrenocorticotropic Hormone↗
PubMed1981

Pars intermedia peptides: studies in adult humans.

A combination of radioimmunoassays and chromatography under acid-dissociating conditions has been used to obtain profiles of ACTH and LPH-related peptides in human plasma and cerebrospinal fluid. The spectra of peptides observed in these two fluids differ markedly. ACTH, beta-LPH, gamma-LPH and beta-endorphin are observed in the plasma of normal subjects and patients with increased pituitary ACTH secretion, whereas cerebrospinal fluid contains ACTH, beta-LPH, gamma-LPH and beta-endorphin, a 31 000-molecular-weight putative precursor having ACTH, LPH and gamma-MSH immunoreactivities, as well as pro-gamma-MSH(1-77) and smaller immunoreactive gamma-MSH fragments, alpha-MSH was not observed in blood or cerebrospinal fluid but this pars intermedia peptide and corticotropin-like intermediate lobe peptide (CLIP) were both found in tumour tissues obtained from patients with the ectopic ACTH syndrome. In vitro studies of human pituitary tumour tissues confirmed concomitant secretion of ACTH, beta-LPH, gamma-LPH, beta-endorphin and pro-gamma-MSH, which could be stimulated by a preparation of crude stalk median eminence and synthetic arginine vasopressin, from the rat, and could be suppressed by hydrocortisone. Clinical studies in which electroacupuncture was used to alleviate the symptoms of heroin withdrawal or recurrent pain revealed that concentrations of met-enkephalin and beta-endorphin, respectively, may rise in cerebrospinal fluid in association with relief of symptoms.

Adrenocorticotropic Hormone↗
PubMed1981

The effect of naloxone on pulsatile gonadotrophin release in normal subjects.

The gonadotrophin response to naloxone infusion has been investigated in three adult males, and three adult females in the early follicular phase. The frequency of LH secretory episodes and the mean LH levels increased in both sexes. The data suggest that the pulsatile release of LH is under inhibitory opiate control.

Adult↗
PubMed1981

The opioid control of LH and FSH release: effects of a met-enkephalin analogue and naloxone.

The effect of long-acting analogue of met-enkephalin (DAMME) and naloxone on gonadotrophin secretion has been investigated in man. In menopausal women DAMME induced a progressive fall in LH to approximately 60% of basal levels at 3 h, which was blocked by naloxone; there was a smaller fall in FSH that did not attain statistical significance. However, the LHRH-induced rise in LH and FSH in young male volunteers was unaffected by pretreatment with a high-dose DAMME infusion. Naloxone infusion in young male and female normal subjects produced a significant rise in both LH and FSH. Long-term infusion of naloxone appeared to increase the rate, and possibly the amplitude, of LH pulsatility. These results suggest that met-enkephalin-like opioid peptides exert a tonic inhibitory control of LH release in both menopausal and young subjects of both sexes. This control is most likely to be at the level of the hypothalamus, and involves modulation of pulsatile LHRH release.

Adolescent↗
PubMed1981

Studies off the opiate control of prolactin, GH and TSH.

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.

Adolescent↗
PubMed1981

Prolactin pulsatility in patients with gonadal dysfunction.

Serum prolactin concentrations have been measured at 15 min intervals for 2 h on 240 occasions in 227 patients with symptoms which could have been due to hyperprolactinaemic gonadal dysfunction. Of the 227, 138 had at least one elevated random prolactin level. Overall, 22% showed no significant fluctuation in prolactin. In 38% the levels fell progressively from the start of the sampling period, this pattern being found most commonly in patients complaining of infertility. The sampling method yielded a basal or unstressed prolactin concentration which was, on average, 27% lower than random prolactin concentrations. However, a comparison with clinical data, the radiological appearances of the pituitary fossa, and the response to bromocriptine therapy, has shown that there is no predictive information in the multiple sampling results that could not have been obtained from two or three random prolactin levels.

Blood Specimen Collection↗
PubMed1981

The effects of a met-enkephalin analogue on ACTH, beta-LPH, beta-endorphin and MET-enkephalin in patients with adrenocortical disease.

Thirteen patients with either Addison's disease, or Cushing's disease treated by bilateral adrenalectomy, were infused with the long-acting met-enkephalin analogue DAMME. In patients with Addison's disease significant and pronounced falls in ACTH and N- and C-terminal beta-LPH were seen; chromatography suggested that beta-endorphin fell concomitantly. Three out of four patients with Cushing's disease who had not received pituitary irradiation, also showed a decrease in plasma ACTH and N- and C-terminal beta-LPH; however, no change was seen in any of the irradiated patients. The changes were naloxone reversible. The levels of plasma met-enkephalin were normal and did not change after DAMME in any group of patients. These results are interpreted as suggesting that there are inhibitory opiate receptors controlling the release of ACTH, beta-LPH, and beta-endorphin.

Addison Disease↗