The neuroendocrinology of opioid peptides.
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Adrenocorticotropic Hormone↗
Biomedical subjects
L H Rees
Publications and source records attributed to L H Rees.
Male gonadal function in coeliac disease: III. Pituitary regulation.
Pituitary regulation of gonadal function was investigated in 39 consecutive men with treated and untreated coeliac disease and in an intestinal disease control group of 19 men with Crohn's disease of similar age and general nutritional status. Basal serum FSH concentration was increased in 10 of the coeliacs (26%) compared to only two of 19 men with Crohn's disease (11%). This abnormality was observed with equal frequency in both treated and untreated coeliacs, and was not associated with oligospermia. Serum LH concentration was increased in eight of 15 untreated coeliacs (53%) with sub-total villous atrophy, an abnormality which unlike the elevation of serum FSH, appears to return towards normal after gluten withdrawal. Serum LH was high in coeliacs despite marked elevation of the free testosterone index. Exaggerated responses of FSH and LH to LHRH were found in 89% and 45% respectively, of coeliacs with sub-total villous atrophy. However, exaggerated responses of LH alone were found more frequently in coeliacs than in men with Crohn's disease (P less than 0.02) and unlike the exaggerated FSH responses, LH responses were closely related to jejunal morphology. Exaggerated responses of FSH and LH in coeliacs were commonly found when basal gonadotrophin concentrations were normal. The occurrence of exaggerated gonadotrophin responses could not be related to plasma concentration of testosterone, dihydrotestosterone, oestradiol or the free testosterone index. Serum prolactin was modestly raised in 25% of untreated and partially treated coeliacs and in the same proportion of men with Crohn's disease. Elevated serum prolactin concentrations never exceeded 809 mU/l and were not associated with impotence or infertility. This study provides further evidence that in men with coeliac disease there is a derangement of pituitary regulation of gonadal function. This would seem to be part of a wider disturbance of central regulatory mechanisms of endocrine function in coeliac disease.
Adolescent↗
Pro-opiocortin related peptides in human pituitary and ectopic ACTH secreting tumours.
Basal and stimulated secretion of N-terminal pro-opiocortin (Pro-gamma-MSH), ACTH and LPH from seven pituitary and three ectopic ACTH secreting tumours have been studied in vitro using a perfused isolated cell system. The peptides were shown to be released concomitantly and in equimolar amounts. The pituitary tumours responded to stimulation with rat stalk median eminence extracts (SME) and synthetic AVP. However, peptide release from the ectopic tumours, although pulsatile, remained autonomous. Prior to surgery, gel-chromatographic profiles of plasma immunoreactive ACTH showed only one peak, which eluted in the position of 1-39 ACTH, in patients with the pituitary tumours, but there was a second peak of large molecular weight ACTH present in the plasma from those with the ectopic ACTH syndrome. This second form of ACTH could not be detected in any of the tumour cell column effluents. An eighth pituitary tumour was atypical, in its unusually large size, clinically aggressive nature and spectrum of peptide release. Although peptide release in response to stimulation with SME was similar to that observed with the other pituitary tumours, the chromatography of the plasma ACTH resembled the ectopic plasma pattern, showing two peaks of immunoreactivity.
ACTH Syndrome, Ectopic↗
Endogenous opioid peptides in pregnancy.
Plasma levels of two endogenous opioid peptides, beta-endorphin and met-enkephalin, as well as immunoreactive N-terminal beta-lipotrophin (N-LPH) were studied in normal pregnant women from 8 to 41 weeks gestation. A total of 116 samples were assayed for beta-endorphin-like immunoreactivity (C-LPH), 103 for N-LPH and 75 for met-enkephalin. Plasma beta-endorphin-like immunoreactivity and N-LPH levels rose progressively throughout gestation and reached a maximum at term. Plasma met-enkephalin immunoreactivity did not significantly change throughout pregnancy. These results reflect an increasing and consistent adrenocorticotrophin (ACTH)/beta-LPH and beta-endorphin secretion throughout pregnancy, while the unchanged met-enkephalin levels are compatible with its known derivation from a separate precursor system.
Endorphins↗
Male gonadal function in coeliac disease: 2. Sex hormones.
Hypogonadism, infertility, and sexual dysfunction occur in some men with coeliac disease. We have measured plasma testosterone, dihydrotestosterone, sex-hormone binding globulin, oestradiol, and serum luteinising hormone in 41 men with coeliac disease and have related these findings to jejunal morphology, fertility, semen quality, and sexual function. To determine the specificity of these observations in coeliacs we also studied 19 nutritionally-matched men with Crohn's disease, and men with chronic ill-health due to rheumatoid arthritis and Hodgkin's disease. The most striking endocrine findings in untreated coeliacs were increased plasma testosterone and free testosterone index, reduced dihydrotestosterone (testosterone's potent peripheral metabolite), and raised serum luteinising hormone, a pattern of abnormalities indicative of androgen resistance. As jejunal morphology improved hormone levels appeared to return to normal. This specific combination of abnormalities was not present in any of the disease control groups and, to our knowledge, androgen resistance has not been described previously in any other non-endocrine disorder. Plasma oestradiol concentration was modestly raised in 10% of coeliacs and 11% of patients with Crohn's disease. Unlike plasma androgens and serum luteinising hormone in coeliacs, plasma oestradiol was not clearly related to jejunal morphology. Androgen resistance and associated hypothalamic-pituitary dysfunction appear to be relatively specific to coeliac disease and cannot be explained merely in terms of malnutrition or chronic ill-health. In addition, our findings suggest that this endocrine disturbance may be related to sexual dysfunction in coeliac disease but its relationship to disordered spermatogenesis in this condition has not been clearly established.
Adolescent↗
Dopaminergic control of the rat thyrotroph.
The established technique of dynamic perfusion of dispersed rat anterior pituitary cells was used to investigate the role of dopamine in the release of thyroid-stimulating hormone (TSH). The basal release of TSH was 124 +/- 22 ng/ml (mean +/- SEM) and this remained unchanged in the presence of dopamine (5 X 10(-6) M), while basal prolactin release was suppressed to 50% of control values. Perfusion with thyrotrophin-releasing hormone (TRH) in doses between 1.4 X 10(-10) and 22.4 X 10(-10) M produced a consistent and reproducible dose-response curve for TSH (n = 14) which was not significantly altered by the presence of dopamine (n = 5). Perfusion with bromocriptine (10(-6) M), a dopamine agonist, did not alter the basal or stimulated TSH release. No stimulation of TSH release was observed when the cells were challenged with 2-min pulses of domperidone, a dopamine antagonist (2 X 10(-9) to 2 X 10(-5) M). The inclusion of somatostatin-14 (3 X 10(-9) M) in the perfusate inhibited TRH-stimulated TSH release. Our results suggest that, in the rat, dopaminergic inhibition of TSH release does not occur at the level of the pituitary.
Animals↗
Bromocriptine improves reduced libido and potency in men receiving maintenance hemodialysis.
Twenty-five men on maintenance hemodialysis commenced a placebo-controlled, double-blind, crossover trial of bromocriptine for erectile impotence. Eight patients on bromocriptine and one on placebo failed to complete the trial due to side-effects and 2 were withdrawn following renal transplantation. Libido or the frequency and/or quality of erections or both improved in 11 of the remaining 14 patients during bromocriptine treatment. A significant (P less than 0.01) improvement in patients' perception of sexual performance occurred on bromocriptine compared with placebo. The 3 patients in whom potency failed to improve had the lowest serum testosterone concentrations. Bromocriptine is usually effective in the management of impotence in males receiving maintenance hemodialysis provided pretreatment serum testosterone is above the lower end of the normal range, but side-effects are relatively common.
Adult↗
Corticotropin-releasing factor immunoreactivity in human gastrointestinal tract.
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Corticotropin-Releasing Hormone↗
Gonadal function in Hodgkin's disease: long-term follow-up of chemotherapy.
A long-term study of gonadal function was conducted in 46 men and 28 women in prolonged remission of advanced Hodgkin's disease after cyclical combination chemotherapy with nitrogen mustard, vinblastine, prednisolone, and procarbazine. The mean follow-up was 6.9 years. Azoospermia or profound oligospermia occurred in 36 of the men, but late recovery was occasionally observed. Testosterone secretion was preserved. Amenorrhoea and gonadal hormone deficiency developed in 22 of the women and never recovered. Partial or complete chemical sterilisation and gonadal hormone deficiency is currently a consequence of cure of advanced Hodgkin's disease in most patients.
Adolescent↗
Bromocriptine in management of large pituitary tumours.
Bromocriptine has an accepted place in the management of small pituitary tumours that secrete either prolactin or growth hormone. The treatment of large tumours with extrasellar extensions is more difficult, however: though surgery is the standard treatment, it is often unsuccessful in returning excessive hormone secretion to normal and may cause hypopituitarism. A prospective trial was undertaken to assess the frequency with which changes in pituitary function and size of large tumours occurs. Nineteen patients were studied before and during treatment with bromocriptine (7.5 to 60 ml/day) for three to 22 months, using contrast radiology and a detailed assessment of pituitary function. Eighteen patients had hyperprolactinaemia and two of these also had raised concentrations of growth hormones; one patient had an apparently non-functioning tumour. In 12 patients (63%) tumour size decreased with bromocriptine and no tumour enlarged. Nine patients had visual-field defects, which improved in seven, becoming normal in five. Pituitary function improved in nine patients (47%) becoming entirely normal in three. Bromocriptine should be the treatment of choice in patients with large pituitary tumours with extrasellar extensions, provided close supervision is maintained.
Adult↗
New hypothalamic hormone, corticotropin-releasing factor, specifically stimulates the release of adrenocorticotropic hormone and cortisol in man.
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Adrenocorticotropic Hormone↗
Oral contraception in patients with hyperprolactinaemia.
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Adult↗
Experience with selective venous sampling in diagnosis of ACTH-dependent Cushing's syndrome.
Twenty-three patients with adrenocorticotrophic hormone-(ACTH)-dependent Cushing's syndrome were subjected to selective venous catheterisation and sampling for ACTH on a total of 26 occasions. Out of 10 patients with pituitary-dependent disease, nine had raised ACTH concentrations in one or both high internal jugular vein samples. Eight patients had 11 proved sites of ectopic hormone production: of these, six were correctly identified by the sampling technique, and in four of them this was the only accurate method of localisation. The results of one catheterisation were misleading, and on 10 occasions they were inconclusive; five patients remained undiagnosed by any method. Overall, 15 of the 26 catheterisations provided diagnostically valuable information. Selective venous catheterisation and sampling for ACTH is effective in confirming a pituitary source of the hormone and may be valuable in locating the source of ectopic ACTH production in some cases.
ACTH Syndrome, Ectopic↗
Simultaneous release of neurotensin, somatostatin, enkephalins and catecholamines from perfused cat adrenal glands.
Acid extracts of cat adrenal medullae were found to contain neurotensin-like (0.71 +/- 0.21nmol/gm), met-enkephalin-like (11.71 +/- 2.87nmol/gm), leu-enkephalin-like (1.95 +/- 0.11nmol/gm) and somatostatin-like (1.57 +/- 0.63pmol/gm) immunoreactivities. Using isolated retrogradely perfused cat adrenal glands the secretory responses to acetylcholine (ACh), nicotine and potassium ions (K+) were studied. Spontaneous secretion of catecholamines, neurotensin-like, met-enkephalin-like, leu-enkephalin-like and somatostatin-like immunoreactivities was negligible. However, ACh (5.5 X 10(-5)M), nicotine (2.2 X 10(-5)M) and 55mM K+ all evoked the simultaneous release of noradrenaline, adrenaline and the four neuropeptide immunoreactivities. The ACh stimulated secretion of the four neuropeptides could be prevented by perfusion with hexamethonium (C6, 2.8 X 10(-4)M). The concomitant release of these neuropeptides with catecholamines suggests that they may have a role in the modulation of stress responses.
Acetylcholine↗
Tamoxifen, aminoglutethimide and danazol: effect of therapy on hormones in post-menopausal patients with breast cancer.
Gonadotrophins, oestradiol, androstenedione, testosterone and dehydroepiandrosterone sulphate (DHAS) were measured sequentially in 72 patients with advanced breast cancer receiving endocrine therapy of various types. Tamoxifen significantly reduced gonadotrophins but did not effect other hormones. Danazol also reduced gonadotrophins. Aminoglutethimide (AGT) reduced oestradiol and DHAS but had not effect on gonadotrophins. The effects of administering tamoxifen, AGT and danazol together (TAD) together were therefore examined. This combination reduced gonadotrophins, oestradiol and DHAS, but no further than tamoxifen and AGT alone. The degree and duration of hormone suppression were similar in both responders and non-responders to tamoxifen, AGT or TAD, though patients responding to AGT showed more complete suppression at the end of the course of treatment, perhaps because they were treated longer. On relapse, adequate gonadotrophin and steroid suppression was demonstrated in patients receiving tamoxifen and AGT respectively. We conclude that (a) response to endocrine therapy is unlikely to be related to the degree of endocrine suppression produced by the therapy; (b) combination endocrine therapy does not further reduce serum-hormone concentrations and (c) relapse is unlikely to be due to escape from the hormone-inhibitory effects of endocrine agents.
Aminoglutethimide↗
Circulating testosterone, sex hormone binding globulin and prolactin in women with late onset or persistent acne vulgaris.
Serum testosterone, sex hormone binding globulin (SHBG) and prolactin were measured in thirty-eight women with acne which persisted or started after the age of 18 years. One or more of these levels were abnormal in 76% of patients. Increased testosterone or low SHBG were present alone or in combination in 60% of patients. This group was presumed to have a raised level of non-protein bound, metabolically-available testosterone. Hyperprolactinaemia, which was present in 45% of patients, may be important in view of the reported association with increased adrenal androgens. The hormonal abnormalities may be causally related to the acne and a greater understanding of them may lead to better treatment.
Acne Vulgaris↗
The role of opiate peptides in the control of prolactin in the puerperium, and TSH in primary hypothyroidism.
The role of endogenous opiate peptides in puerperal hyperprolactinaemia, and in the control of TSH in hypothyroidism, has been investigated. Although exogenous opioids raise prolactin and TSH levels, 16 mg naloxone administered to women on days 2-4 of the puerperium produced no significant change in serum prolactin and the same dose of naloxone had no significant effect on serum TSH in six primary hypothyroid patients. There is little evidence that endogenous opioid peptides are major modulators of prolactin or TSH in man under these conditions.
Endorphins↗
Recovery of hypothalamo-pituitary-adrenal function in asthmatics whose oral steroids have been stopped or reduced.
Hypothalamo-pituitary--adrenal (HPA) function was studied using tetracosactrin and insulin hypoglycemia tests in eleven asthmatic patients who were receiving or had taken oral steroids. The patients had been on prednisone, 5--20 mg/day for 2--17 years. As the dose was reduced they used beclomethasone inhalation, up to 800 micrograms/day. Seven insulin hypoglycemia tests were performed when the patients had been off oral steroids for 15--37 months. Plasma cortisol responses were normal in all seven, three had subnormal responses of ACTH. In five patients serial tetracosactrin and insulin hypoglycaemia tests were performed during reduction of steroid dose. Two patterns of recovery of HPA function were observed. In one, both hypothalamo--pituitary and adrenal function seemed to return simultaneously, in the other normal response to tetracosactrin appeared before that to insulin hypoglycaemia. One patient had normal ACTH and cortisol responses to the stress of a vasovagal attack, but failed to respond to subsequent hypoglycaemia. We conclude that a normal response to tetracosactrin does not indicate recovery of the HPA axis after stopping prolonged oral steroid therapy for asthma, and that patients should continue to carry steroid therapy cards for at least 5 years after such treatment has been discontinued.
Adrenocorticotropic Hormone↗