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W. M. HUNTER and W. M. RIGAL

SUMMARY

The diurnal pattern of plasma growth hormone levels has been investigated in nine children, without endocrinopathy, aged 8–15 yr., from whom blood samples were taken hourly during the day and 2-hourly at night.

Growth hormone was undetectable (< 1 μmg./ml.) during the first 2 hr. after meals but the levels rose thereafter to values many times higher than those found in adults. High values were consistently encountered during the night.

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W. M. HUNTER and J. G. BENNIE

Serum and plasma from human and domestic animals contain variable amounts of non-specific material(s) which may be mistaken for hormone in assays for human LH and FSH, based upon antisera of high sensitivity and hormonal monospecificity. The non-specific response curves are generally, but not invariably, less steep than those of the hormone standards and endogenous homologous hormones. The levels of non-specific intrusion can be of sufficient magnitude to obscure specific estimations seriously, particularly at low hormone levels, unless the assays are designed to minimize this effect.

The non-specific effects could be minimized (but not abolished) by careful optimization of the assays which involved making the response curve as sensitive as possible and incorporating the serum at a final dilution of 1: 2, since further dilution increased the relative contribution of the non-specific substance(s). The optimized assays require only 48 h of total incubation and show a sevenfold increase in the mean concentration of LH between sera from prepubertal children and adults accompanied by a mean threefold difference in the concentration of FSH.

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H. K. AMIN and W. M. HUNTER

SUMMARY

The volume of distribution, plasma clearance and urinary recovery of human follicle-stimulating hormone (FSH) after intravenous injection has been estimated in healthy men. A human FSH-anti FSH radioimmunoassay was used which, though not completely specific, discriminates against luteinizing hormone (LH) by at least 10:1 in terms of i.u.

The half-life in the circulation was 24–38 min in three subjects who received the same dose. Urinary recovery, when expressed as a percentage of the injected dose, was 36·8 ± 7·7 (s.d.)% in nine experiments with three different doses in six subjects. The time-course and percentage recovery were similar for all doses used.

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A. D. TOFT, W. M. HUNTER and W. J. IRVINE

It has been established in animals that anterior pituitary hormones control their own secretion by regulating at a hypothalamic level the release of their hypothalamic factors (Motta, Fraschini & Martini, 1969). If a negative 'short-feedback' of thyroid-stimulating hormone (TSH) on the hypothalamus exists in man, the high plasma TSH levels of untreated primary hypothyroidism should fall markedly after the administration of bovine TSH which shares the biological, but not the immunological, properties of human TSH. This report describes the effects of bovine TSH on human plasma TSH (H-TSH) levels in patients with primary hypothyroidism.

Twenty-seven patients with untreated primary hypothyroidism were studied, of whom 20 had been treated with 131I and four by subtotal thyroidectomy for thyrotoxicosis. The remaining three patients had spontaneous primary hypothyroidism. The diagnosis of primary hypothyroidism was made on clinical grounds and on the basis of a low serum protein-bound iodine (< 3·8 μg/100 ml),

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W. M. HUNTER, J. M. T. WILLOUGHBY and J. A. STRONG

SUMMARY

Plasma insulin and growth hormone were measured by radioimmunoassay in healthy adults during the latter part of 22 hr. fasts and after graded glucose loads. The insulin concentration was less than 8 μ-u./ml. in all fasting samples and in samples taken after the blood glucose had returned to fasting levels. Insulin levels increased with increasing glucose loads.

During fasting, growth hormone showed intermittently raised secretion; in some subjects high values were reached at times which could not be related to external events or to stress. Growth hormone levels were consistently low during the absorption of glucose but rose immediately thereafter. This rise occurred increasingly late and reached increasing levels as the glucose loads were made progressively larger.

Insulin had almost invariably returned to fasting levels before the growth hormone concentrations began to rise.

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W. M. HUNTER, J. A. R. FRIEND and J. A. STRONG

SUMMARY

Plasma growth hormone (GH) levels were measured at intervals throughout the day in various subjects. Several healthy men showed increased levels 3–4 hr. after a meal. Plasma GH was generally low in obese subjects with or without diabetes. Four acromegalic patients had consistently and markedly raised levels which were unaffected by food. In two thyrotoxic patients GH values were not different from normal.

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F. C. W. Wu, S. M. Borrow, K. Nicol, R. Elton and W. M. Hunter

ABSTRACT

The onset of puberty is characterized by a sleep-associated increase in pulsatile LH secretion which is not observed in adults. The ontogeny of gonadotrophin secretion during pubertal maturation may reflect changes in endogenous LHRH secretion, pituitary sensitivity to LHRH and/or alterations in gonadal steroid feedback. To understand the interplay between these mechanisms, we have examined the pulsatile pattern of plasma LH, FSH, testosterone, oestradiol and prolactin between 20.00 and 09.00 h and the pituitary response to repeated exogenous LHRH stimulation in 16 boys with delayed puberty (age 16·3±2·7 (s.e.m.) years) on one to four occasions in a mixed longitudinal/cross-sectional analysis. Physical maturity was determined by Tanner G staging (1–5) and clinical progress followed for a mean duration of 22·4 ± 8·5 months during which 33 hormone profiles were obtained.

Nocturnal (23.00–09.00 h) LH pulse frequency increased to a peak of 0·54±0·03/h at stage 2 which was followed by a gradual decline to 0·42 ± 0·04/h at stage 5. The appearance of LH pulses in the evening (20.00–23.00 h), probably representative of the rest of the day, was delayed until mid-puberty from which point frequency increased to a peak of 0·53 ±0·08/h at stage 5. LH pulse amplitude showed a linear increase from stages 1 to 5, with nocturnal pulse amplitudes being higher than evening pulses throughout. FSH did not show a clear pulsatile pattern. The LH: FSH ratio reversed from < 1 to > 1 at stage 2. The LH response to exogenous LHRH increased in parallel with LH pulse amplitude. There was no difference in the pattern of LH response to repeated LHRH stimulation as puberty advanced; the first stimulus always elicited a greater response than subsequent doses. In contrast, the FSH response to LHRH was maximal at stage 1 and became attenuated thereafter. The estimated mean nocturnal LHRH concentration or amplitude did not show any increase during pubertal maturation from 20·42±11·57 at stage 1 to 35·96 ± 20·83 ng/l at stage 5.

In conclusion, the sequential changes in this study suggest that the sleep-entrained increase in LHRH pulse frequency plays a key role at the onset of puberty. By enhancing pituitary responsiveness and setting in motion a cascade of events, this peripubertal augmentation of LHRH pulse frequency can account for most of the subsequent changes in LH, FSH and testosterone secretion during pubertal development in the male without any apparent alteration in LHRH pulse amplitude.

Journal of Endocrinology (1989) 123, 347–359

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LIISI ADAMSON, W. M. HUNTER, O. O. OGUNREMI, I. OSWALD and I. W. PERCY-ROBB

SUMMARY

The effects of strenuous daytime physical exercise were examined in 12 healthy male volunteers. All-night electrophysiological recordings were made and blood was sampled during sleep by indwelling venous catheter.

Plasma growth hormone levels were significantly increased after exercise but the sleep electroencephalographic patterns of nights after exercise did not differ significantly from those of control nights. Plasma corticosteroids were decreased after exercise. It is suggested that higher levels of growth hormone are consistent with reparative processes during sleep.

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K. P. McNATTY, W. M. HUNTER, A. S. McNEILLY and R. S. SAWERS

SUMMARY

The concentrations of FSH, LH, prolactin, oestradiol and progesterone were measured in peripheral plasma and follicular fluid of women throughout the menstrual cycle. With the exception of prolactin, concentrations of pituitary and steroid hormones in follicular fluid correlated with those in peripheral plasma.

Follicle-stimulating hormone was present in a greater number of small follicles ( < 8 mm) during or just after the peaks of FSH in peripheral plasma. During the mid-follicular phase the concentration of both FSH and oestradiol in fluid from large follicles ( ≥ 8 mm) was high. During the late follicular phase the large follicles ( ≥ 8 mm) contained high amounts of progesterone in addition to oestradiol, low physiological levels of prolactin, and concentrations of LH and FSH about 30 and 60% respectively of those found in plasma. By contrast no large 'active' follicles ( ≥ 8 mm) were found during the luteal phase although many contained both LH and FSH. Luteinizing hormone was present in a proportion of small follicles ( < 8 mm) during the late follicular and early luteal but not at other stages of the menstrual cycle.

It is suggested that a precise sequence of hormonal changes occur within the microenvironment of the developing Graafian follicle; the order in which they occur may be of considerable importance for the growth of that follicle and secretory activity of the granulosa cells both before and after ovulation.

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W. M. HUNTER, F. J. GILLINGHAM, P. HARRIS, J. A. KANIS, F. M. McGURK, J. McLELLAND and J. A. STRONG

SUMMARY

Assays for human growth hormone (HGH) were carried out on 89 acromegalic patients, 81 of whom were studied before any treatment had been given. Serial studies were undertaken, generally at 6-monthly intervals, with the same test procedure, using a 50 g oral glucose tolerance test (GTT) and identical assay conditions over a period of 8 years. Twenty-three patients were assessed at intervals during periods of up to 4 years whilst they remained untreated. The general picture was one of unchanging HGH levels.

Ten patients were studied before and after external irradiation. HGH levels showed a slow continuing fall for as long as 4 years and thereafter they stabilized at one-third of pretreatment values. HGH levels in 12 patients treated with radioactive implants showed an immediate fall to one-third, and thereafter a further slow decline to one-tenth of pretreatment levels. The response in eight patients treated by surgical removal of pituitary tissue and subsequent radiotherapy varied considerably.

No patient, treated or untreated, showed evidence of partial suppression of HGH secretion during the GTT although three patients consistently responded to glucose with paradoxical hypersecretion.