W. J. Jeffcoate

HORMONAL AND METABOLIC RESPONSES TO AN ENKEPHALIN ANALOGUE IN NORMAL MAN

An enkephalin analogue [D-Ala2, MePhe4, Met(o)-ol] enkephalin (DAMME), given intravenously to normal subjects raised serum prolactin and growth-hormone levels but lowered serum levels of luteinising hormone, follicle-stimulating hormone, cortisol, and corticotrophin. There was also a small fall in total glucagon and gastric inhibitory peptide (G.I.P.) and a rise in thyrotrophin. beta-Lipotrophin, motilin, vasoactive intestinal peptide, insulin, gastrin, and pancreatic glucagon were unchanged. Blood-glycerol increased, and blood lactate, alanine, and glucose fell. Prior administration of the opiate antagonist, naloxone, attenuated the hormonal responses to DAMME. This enkephalin analogue produces endocrine and metabolic changes in man which may be mediated through opiate-binding receptors both within and outside the brain. The enkephalins and related substances may provide an important link between perception, behaviour, and neuroendocrine regulation of hormone secretion and metabolism.

β-ENDORPHIN IN HUMAN CEREBROSPINAL FLUID

beta-endorphin is a brain peptide with potent morphine-like activity structurally related to the anterior pituitary hormone beta-lipotrophin (beta-L.P.H.). We have developed a radioimmunoassay for human beta-endorphin in plasma and cerebrospinal fluid (C.S.F.). Since the antiserum also reacts with beta-L.P.H., beta-endorphin was distinguished by using a second antiserum which measures beta-L.P.H. alone. With these two immunoassay systems and gel chromatography, we found beta-endorphin in all 20 C.S.F. samples tested at a concentration always higher than, but with no other relationship to, that in plasma. beta-endorphin was found in C.S.F. of patients who had hypopituitarism and undetectable plasma-beta-endorphin, suggesting that it is synthesized in the brain rather in the pituitary.

ENDOCRINE FUNCTION IN THE PRADER‐WILLI SYNDROME

Hypothalamic, pituitary and gonadal function was studied in five male and three female patients with the Prader‐Willi syndrome. All were clinically hypogonadal: all males had low circulating testosterone levels, although in two females basal plasma oestradiol was within the normal range for the early follicular phase of the menstrual cycle. Basal gonadotrophin levels were low and the response to the intravenous administration of LHRH was subnormal in seven. Repeat administration of LHRH after 10 days and 6 weeks treatment with oral clomiphene (200 mg daily) was followed by a normal rise in luteinizing hormone (LH) and follicle stimulating hormone (FSH) in four out of five patients tested. All five males were tested with human chorionic gonadotrophin (hCG) and the rise in plasma testosterone was subnormal in four. Treatment with hCG was continued for 6 weeks in these four patients, but in only one did testosterone levels rise (transiently) to the normal adult male range. In one female patient studied no rise in plasma oestradiol was detected in response to human menopausal gonadotrophin (hMG). These results suggest that the hypogonadism in the Prader‐Willi syndrome is due to combined hypothalamic and primary gonadal abnormalities.

THE CIRCADIAN VARIATION OF IMMUNOREACTIVE LIPOTROPHIN AND ITS RELATIONSHIP TO ACTH AND GROWTH HORMONE IN MAN

There is a clear circadian rhythm of plasma immunoreactive LPH in man with the trough occurring between 22.00 h and 03.00 h and the peak between 07.00 h and 08.00 h, immediately after waking. At all times circulating LPH and ACTH levels follow each other closely. However, no correlation was observed between LPH levels and either plasma GH or the stage of sleep.

THE EFFECT OF CYPROTERONE ACETATE ON SERUM TESTOSTERONE, LH, FSH, AND PROLACTIN IN MALE SEXUAL OFFENDERS

The anti‐androgen, cyproterone acetate, was administered in a dose of 100 mg/day to eight adult male sexual offenders for 21–31 days. Serum testosterone fell to subnormal levels within 7 days and remained low for 6–28 days after treatment was stopped. The fall in testosterone was accompanied by a fall in serum luteinizing hormone (LH) and follicle stimulating hormone (FSH), and a rise in serum prolactin. All subjects experienced a decrease in libido and in frequency of masturbation. The probable mechanisms of action of cyproterone acetate are discussed, as is its potential role in the management of sexual offenders. These studies suggest that measurement of serum testosterone could be used as an index of compliance in sexual offenders treated with cyproterone acetate who are released on parole.

COMPARISON OF THE PHARMACOKINETICS IN MAN OF TWO SYNTHETIC ACTH ANALOGES: a1–24 AND SUBSTITUTED β1–18 ACTH.

The synthetic substituted corticotrophin analogue, a1–18 ACTH, was given intravenously or subcutaneously to thirteen human volunteers in whom endogenous secretion of ACTH had been suppressed with dexamethasone. Plasma levels of a1–18 ACTH over the succeeding 12–24 h were determined by radioimmunoassay and bioassy, together with the fluorometric corticosteroid responses. The plasma disappearance rate of a1–18 ACTH was compared with that of the corticotrophin fragment, a1–24 ACTH (tetracosactrin, Synacthen), in both unmodified and depot forms.

Adrenocorticotropin and Related Peptides in Nonendocrine Tumors

Publisher Summary This chapter focuses on adrenocorticotropin and related peptides in nonendocrine tumors. The ectopic adrenocorticotropic hormone (ACTH) syndrome is usually defined as the secretion of ACTH and/or of closely related peptides, by a tumor comprised of cells that are not normally engaged in their production. It is the syndrome that results from ACTH secretion by a nonpituitary tumor. It has been established beyond doubt that tumors of certain groups of cells frequently synthesize and secrete ACTH, its precursor forms, or its fragments. The synthesis of ACTH in such tumors is common and includes at least 50% of all oat cell carcinomas of the lung. The formation and secretion of ectopic ACTH is probably invariably accompanied by the formation of β n -LPH-related peptides. The chapter discusses the diagnosis, clinical features, and incidence of ectopic ACTH syndrome, characterization of ectopic ACTH and related peptides, tumor types associated with ectopic ACTH secretion, and ACTH and related peptides in control tumors.