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ABSTRACT
We have studied the effect of dopamine together with agonist and antagonist drugs of different specificities on the release of TRH from the perfused, intact hypothalamus of the adult rat in vitro. Dopamine produced a dose-related stimulatory effect on TRH release with maximal effect being achieved at 1 μmol/l (increase over basal, 118 ±16·5 (s.e.m.) fmol TRH; P <0·001 vs basal). This effect was mimicked by the specific D2-agonist drugs bromocriptine (0·1 μmol/l) and LY 171555 (0·1 μmol/l) (increase over basal values, 137·5±13·75 fmol and 158·6± 10·7 fmol respectively; P <0·001 vs basal), but not by the D1-agonist SKF 38393A. The stimulatory effect of dopamine (1 μmol/l) was blocked in a stereospecific manner by the active (d) but not by the inactive (l) isomers of the dopamine antagonist butaclamol. Similar blockade was achieved with the specific D2-antagonist domperidone (0·01 μmol/l) whereas the D1-antagonist SCH 23390 was only effective when used at a concentration 100 times greater. Lower concentrations (0·01 μmol/l) of this D1 -antagonist did not block the stimulatory effect of dopamine. High-performance liquid chromatography characterization of the material secreted within the hypothalamus showed one single peak of immunoreactive material which coeluted with synthetic TRH. These data suggest that dopamine exerts a stimulatory role in the control of hypothalamic TRH release by acting at specific D2-receptors.
J. Endocr. (1987) 115, 419–424
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ABSTRACT
Tammar wallabies (Macropus eugenii) were observed for 7 days, 24 h/day, at the expected time of birth in two consecutive breeding seasons. Blood was collected from the lateral tail vein 1–2 days before birth, then at 10- to 20-min intervals in the peripartum period and less frequently to 30-h post partum. Plasma was assayed for the prostaglandin metabolite 13, 14-dihydro-15-oxo-prostaglandin F2α (PGFM), progesterone and LH. An assay for PGFM was validated which allows direct measurement in 100 μl unextracted plasma with a sensitivity of 0·14 nmol/l (50 pg/ml).
There was a short-lived peak of PGFM immediately before or at birth (7·15 ± 2·52 nmol/l; 2536± 892 pg/ml) which declined to less than 0·28 nmol/l (100 pg/ml) within 2-h post partum. Progesterone concentrations declined about the time of birth, coincident with the peak of PGFM, and reached levels observed in lactationally quiescent animals by 16-h post partum, which was also the time of the LH peak. The transient prostaglandin pulse was detected only by frequent sampling and suggests that, as in other mammals, prostaglandin is important in parturition.
J. Endocr. (1986) 111, 103–109
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Abstract
We have studied the effects of glucose on the release of somatostatin (SS), TRH and GHRH from incubated hypothalami of normal and genetically diabetic, Goto-Kakizaki (GK) rats. The active isomer d-glucose caused a dose-related inhibition of SS, TRH and GHRH from normal rat hypothalami over a 20-min incubation period in vitro. In contrast, in GK rats the effects of glucose on TRH and SS were significantly reduced and the effects on GHRH were abolished. These data indicate that the sensitivity of SS-, TRH- and GHRH-producing hypothalamic neurones is reduced in diabetic rats. The effect is most pronounced for GHRH release as there was no change in the release of this peptide with increasing glucose concentrations. In conclusion, it appears that the diabetic state in GK rats causes differential desensitisation (GHRH>TRH and SS) of neuronal responses to subsequent changes in glucose concentrations in vitro. This may be due to alterations in the neurotransmitter control and/or a reduction in number, affinity or function of glucose transporters on these peptidergic neurones or other intermediary neuronal pathways.
Journal of Endocrinology (1996) 151, 13–17
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ABSTRACT
Effects of thyroid status on brain catecholamine turnover in adult rats were investigated using a steady-state method. Rats were treated for 3 weeks with s.c. injections of l-thyroxine (0·4 mg/kg), aminotriazole in drinking water (0·1%, w/v) or vehicle. After 2 weeks of treatment rats were implanted chronically with lateral intracerebroventricular (i.c.v.) cannulae. They were injected i.c.v. with [3H]tyrosine 1 week later. Catecholamine and tyrosine content and specific activity were measured in mediobasal hypothalamus, anterior hypothalamus and striatum, using high-performance liquid chromatography with electrochemical detection. Thyroxine treatment resulted in a significant increase in noradrenaline and dopamine synthesis localized to the mediobasal hypothalamus. Conversely, aminotriazole treatment resulted in a significant decrease in noradrenaline synthesis localized to the mediobasal hypothalamus. The localization of these changes in catecholamine turnover to the mediobasal hypothalamus suggests that they may be specific functional effects which are of importance in the overall integrated control of thyroid function.
J. Endocr. (1986) 111, 383–389
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SUMMARY
Diced quarter anterior pituitaries from mature female Wistar rats were cultured in synthetic medium with or without added serum. Using each culture as its own control, the thyrotrophin-releasing hormone (TRH) dose–thyrotrophin (TSH) response characteristics of both media were similar; significant TSH secretion being stimulated at TRH doses around 1·5 × 10−9 mol/l. During days 1–3 of culture, basal TSH secretion fell significantly but TRH responsiveness was unchanged. Neither tri-iodothyronine (T3) nor thyroxine (T4) influenced basal TSH secretion.
In both culture media inhibition of TRH responsiveness was demonstrated with concentrations of T3 and T4 within the ranges 1·5 × 10−12 to 1·5 × 10−9 mol/l for T3 and 6·5 × 10−10 to 6·5 × 10−7 mol/l for T4. Equivalent inhibition was accompanied by similar T3 concentrations whether T3 or T4 supplements were used, suggesting that T4 itself has no feedback action. The similar concentrations of T3 required to inhibit TRH responsiveness in media either with or without serum suggest that the pituitary is responsive not only to free but also to total thyroid hormone concentrations, since serum-free medium contains no thyroid hormone-binding protein.
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Naturally occurring diabetogenic substance (NDS), isolated from clinical grade human growth hormone (hGH), induces insulin release from isolated pancreatic islets of hypo-physectomized rats in the presence of Krebs–Ringer bicarbonate solution (KRB) containing 2·8 mmol glucose/l. To determine the role of extracellular glucose in insulin release mediated by NDS, islets were perifused with glucose-free KRB containing 200 μg NDS/ml. Under these conditions NDS induced prompt insulin release (284 ± 34 (s.e.m.)% over basal insulin secretion) (P < 0·0005). Islets perifused with 16·7 mmol glucose/l before and during exposure to 200 μg NDS/ml released additional insulin with exposure to NDS (199 ± 28% over basal insulin secretion) (P< 0·0005). Purified intact hGH (200 μg/ml) did not induce insulin release in the presence of 16·7 mmol glucose/l. Mannoheptulose (5 mmol/l) did not inhibit insulin release mediated by NDS but did inhibit insulin release stimulated by 16·7 mmol glucose/l (P< 0·0005). Islets were pre-incubated for 90 min with 200 μg NDS/ml or 200 μg intact hGH/ml KRB and 2·8 mmol glucose/l to determine what effect either protein might have on subsequent glucose-stimulated (16·7 mmol/l) insulin release. Islets pre-incubated with NDS responded with no less insulin release than islets pre-incubated with intact hGH. Naturally occurring diabetogenic substance initiated insulin release in the absence of extracellular glucose, stimulated additional secretion in the presence of stimulatory glucose concentrations and did not inhibit subsequent islet response to glucose. Naturally occurring diabetogenic substance did not depend on glucose phosphorylation to initiate insulin release.
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ABSTRACT
As part of a controlled trial of the use of tamoxifen for the treatment of mastalgia, some of the metabolic and haematological effects of this agent were measured. A panel of haemostatic variables including prothrombin time, kaolin cephalin clotting time, fibrinogen, euglobulin lysis time, factor VII, factor VIII, protein C and anti-thrombin III were determined. In addition, levels of sex hormone-binding globulin and both total and free oestradiol were estimated. No alteration in clotting function was found during the administration of tamoxifen, although hepatic function did alter during this period with an increase in concentration of sex hormone-binding globulin. There was a significant increase in total oestradiol and free oestradiol although the percentage of biologically available free oestradiol fell slightly during the course of tamoxifen treatment. There was a slight reduction in low-density lipoprotein cholesterol with an increase in HDL2, a subclass of high-density lipoprotein (HDL) cholesterol, consistent with an oestrogen-agonist effect. These data suggest that tamoxifen administration does not adversely influence haemostatic mechanisms or lipoprotein metabolism in the short term.
J. Endocr. (1988) 119, 335–339
