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- Author: M. J. Wheeler x
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ABSTRACT
Peripheral blood samples were collected at 10-min intervals from three conscious sheep in which ovulation had been induced 6–10 days previously using exogenous hormones. Saline was infused into a jugular vein for about 1 h, followed by the experimental drug for 1–2 h and followed by saline again for a further 2 h. The experiments were repeated following induced luteolysis and ovulation. The infusion of a β-adrenergic antagonist (propranolol) into three conscious luteal-phase ewes decreased (P<0·05) the peripheral progesterone concentration in each animal. Infusions of β2-adrenergic agonists (ritodrine and salbutamol) increased (P<0·05) the progesterone concentration in four out of eight experiments. The β-adrenergic antagonist decreased the heart rate and the β2-adrenergic agonist increased it; the arterial blood pressure and respiratory rate were unaffected. The decrease in the prosgesterone concentration in response to the β-adrenergic antagonist suggests that the normal ovarian secretion of progesterone is partly the result of sympathetic stimulation, and that the sympathetic innervation of the ovary may have a physiological role in modulating progesterone secretion.
J. Endocr. (1988) 116, 137–142
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ABSTRACT
It has been shown that the thymus can be regenerated in intact old rats by implanting s.c. a stable analogue of LHRH. Old male rats were given s.c. implants of osmotic pumps containing a solution in citrate buffer of the analogue which was given at a rate of 1 μg/h for 28 days. Some animals were given pumps containing buffer alone, and another group of rats was orchidectomized. The animals were killed after 28 days and the tissues weighed and taken for histology. Serum testosterone was measured by radioimmunoassay.
Sham-treated rats had small fatty thymuses, which were poorly organized with a very narrow band of cortex. Animals treated with the analogue of LHRH and those which had been orchidectomized had relatively large thymuses which were multi-lobed in drug-treated rats, and atrophied accessory sex organs. The testes were grossly atrophied in analogue-treated rats. Histologically, the thymus looked healthy, having a wide, thymocyte-filled cortex and a clearly defined corticomedullary junction. Serum testosterone concentrations were similar in orchidectomized and analogue-treated rats.
It is concluded that it is possible to regenerate the thymus in old rats treated with an analogue of LHRH, but the effect is accompanied by chemical castration. It is also clear that the old pituitary gland is susceptible to the desensitizing action of an LHRH analogue.
J. Endocr. (1987) 112, 345–350
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ABSTRACT
Abnormal ratios of testosterone to epitestosterone (T/E) and testosterone to LH (T/LH) in the urine of male athletes are indicative of testosterone administration. The T/E ratio has been adopted by the International Olympic Committee as the sole criterion used in the detection of testosterone administration. An athlete is usually considered to have failed a drug test if the urinary T/E ratio is greater than 6. Human chorionic gonadotrophin (hCG) has been used by some male athletes to stimulate testicular secretion of testosterone. The purpose of this investigation was to examine whether the urinary T/E ratio can remain unaffected by administration of hCG to normal adult males. Administration of hCG resulted in large increases in serum testosterone concentrations and urinary T/LH ratios but small changes in urinary T/E ratios of two subjects (maximum T/E values observed were 0·8 and 1·2 respectively). These observations suggest that the urinary T/LH ratio is a valuable indicator of hCG as well as of testosterone administration. This study is the first to measure urinary T/LH ratios using the technique of gas chromatography–mass spectrometry for quantification of testosterone, and highly specific monoclonal antibodies for the measurement of LH. An ultrafiltration method is proposed as part of a confirmatory procedure to be adopted in the measurement of urinary gonadotrophins for drug control in sport.
Journal of Endocrinology (1991) 131, 147–154
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ABSTRACT
There are several reports which state that male epileptics on anti-convulsant therapy have reduced sexual activity. We and others have shown that, although total testosterone is raised, the free testosterone concentration is reduced in this patient population. This could be a result of an increased metabolic clearance rate (MCR) of testosterone, inadequate secretion of LH to stimulate testosterone synthesis or inappropriately low testosterone production by the Leydig cells. We have examined these possibilities by measuring the MCR of testosterone in 15 male epileptics on anti-convulsant therapy.
In this group of patients, the mean LH (9·3±5·9 IU/l) and sex-hormone binding globulin (SHBG) (54·5±22·9 nmol/l) concentrations were significantly greater than those of five normal control subjects (4·7±1·11 IU/l and 26·0 ±7·0 nmol/l respectively). Mean total testosterone concentrations of the two groups were not significantly different but the mean percentage of free testosterone and free testosterone concentration were significantly lower in the patient population (2·06±0·43 vs 2·98±0·27 and 0·56±1·1 vs 0·79±0·7 pmol/l). The MCR of testosterone was significantly lower in the patients (773±322 vs 1354±443 1/day) and showed a positive correlation with the percentage of free testosterone. Therefore, our results suggest that the lowered free testosterone in male epileptics on anti-convulsant therapy is not due to an increased MCR of testosterone. The increased LH concentration suggests primary hypogonadism. This, in turn, could be responsible for low free testosterone levels in the presence of normal testosterone.
Journal of Endocrinology (1991) 129, 465–468
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ABSTRACT
The thymus is a critically important organ during development, but atrophies progressively during the ageing process after puberty and is often considered to be unimportant in adult life. We have found that the thymus, which is grossly atrophied in 12- to 15-month-old male rats, is markedly restored in size 30 days after orchidectomy. The organ then appears normal histologically, having a well-defined cortex and medulla, is vascularized and filled with thymocytes. The regeneration of the thymus after orchidectomy was inhibited in a dose–related fashion by testosterone implants which produced serum concentrations of testosterone within the physiological range. The thymus was also increased in size after orchidectomy of 10-week-old rats, and testosterone inhibited the enlargement of the thymus. These results have important implications for the possible enhancement of the immune system with associated improvement of health during ageing and disease. They also point to an important physiological link between the endocrine and immune systems.
J. Endocr. (1986) 110, 417–422
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ABSTRACT
There was no visible thymus in ageing rats of 18 months, and 7 days after orchidectomy there was still no evidence of a thymus. By 30 days after the operation, however, there was a well-defined and well developed bilobular thymus overlying the heart, although it was smaller than those observed in 10-week-old rats. Histologically, the tissue appeared normal, was well vascularized, filled with lymphocytes and several mitotic figures were also seen. When compared with sham-operated animals, blood from these animals had a significantly higher lymphocyte count. These results have important implications for the possible enhancement of the immune system with associated improvement of health during ageing.
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ABSTRACT
In order to investigate the effect of long-term suppression of the gonadotrophin axis in polycystic ovary syndrome, eight affected subjects were given s.c. infusions of gonadotrophin-releasing hormone (GnRH) agonist buserelin for 12 weeks. Hormone measurement and ultrasound studies were carried out weekly, from 6 weeks before to 12 weeks after administration of buserelin. An overnight dexamethasone-suppression test was carried out before and after treatment.
Maximal suppression of LH to below the lower limit of that in normal subjects occurred after 6 weeks of treatment with buserelin. Plasma testosterone and androstenedione fell to normal levels during the infusion but reached pretreatment levels during the follow-up period. There was no effect of buserelin on plasma dehydroepiandrosterone sulphate or sex hormone-binding globulin. Ovarian size decreased significantly during the infusion with the disappearance of cysts in six subjects. After cessation of buserelin therapy, there was rapid and spontaneous ovulation which occurred within 3 weeks in all subjects. The results suggest that treatment with this GnRH agonist facilitates ovulation in this condition.
Journal of Endocrinology (1990) 125, 317–325
Departments of Medicine and Physiology, University of Toronto, 1 Kings College Circle, Toronto, Ontario, M5F 1A8 Canada
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Departments of Medicine and Physiology, University of Toronto, 1 Kings College Circle, Toronto, Ontario, M5F 1A8 Canada
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Departments of Medicine and Physiology, University of Toronto, 1 Kings College Circle, Toronto, Ontario, M5F 1A8 Canada
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Departments of Medicine and Physiology, University of Toronto, 1 Kings College Circle, Toronto, Ontario, M5F 1A8 Canada
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Departments of Medicine and Physiology, University of Toronto, 1 Kings College Circle, Toronto, Ontario, M5F 1A8 Canada
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Departments of Medicine and Physiology, University of Toronto, 1 Kings College Circle, Toronto, Ontario, M5F 1A8 Canada
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Departments of Medicine and Physiology, University of Toronto, 1 Kings College Circle, Toronto, Ontario, M5F 1A8 Canada
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Departments of Medicine and Physiology, University of Toronto, 1 Kings College Circle, Toronto, Ontario, M5F 1A8 Canada
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We investigated whether an increase in cAMP could normalize glucose-stimulated insulin secretion (GSIS) in uncoupling protein-2 (UCP2) overexpressing (ucp2-OE) β-cells. Indices of β-cell (β-TC-6f7 cells and rodent islets) function were measured after induction of ucp2, in the presence or absence of cAMP-stimulating agents, analogs, or inhibitors. Islets of ob/ob mice had improved glucose-responsiveness in the presence of forskolin. Rat islets overexpressing ucp2 had significantly lower GSIS than controls. Acutely, the protein kinase A (PKA) and epac pathway stimulant forskolin normalized insulin secretion in ucp2-OE rat islets and β-TC-6f7 β-cells, an effect blocked by specific PKA inhibitors but not mimicked by epac agonists. However, there was no effect of ucp2-OE on cAMP concentrations or PKA activity. In ucp2-OE islets, forskolin inhibited ATP-dependent potassium (KATP) channel currents and 86Rb+ efflux, indicative of KATP block. Likewise, forskolin application increased intracellular Ca2+, which could account for its stimulatory effects on insulin secretion. Chronic exposure to forskolin increased ucp2 mRNA and exaggerated basal secretion but not GSIS. In mice deficient in UCP2, there was no augmentation of either cAMP content or cAMP-dependent insulin secretion. Thus, elevating cellular cAMP can reverse the deficiency in GSIS invoked by ucp2-OE, at least partly through PKA-mediated effects on the KATP channel.
