Thermogenic effects of thyrotrophin-releasing hormone and its analogues in the rat

Acute or chronic injection of RX 77,368 (a TRH analogue; 1 mg/kg s.c.) stimulated oxygen consumption (VO2) and brown adipose tissue activity in the rat, and decreased weight gain. Other TRH analogues (CG 3509, RGH 2202) and TRH itself also stimulated VO2. These thermogenic actions are probably mediated centrally by stimulation of sympathetic outflow to brown fat.     

Opposite actions of testosterone and progesterone on UCP1 mRNA expression in cultured brown adipocytes

The brown adipose tissue (BAT) thermogenic response to diet-induced obesity and cold has been found to be gender dependent. In the present work, we aimed to investigate the effects of the main physiological male and female sex hormones, i.e. testosterone, progesterone and 17-β-estradiol, on the expression of uncoupling protein 1 (UCP1) – the main mediator of BAT thermogenesis – and on UCP2 and lipid accumulation in rodent brown adipocytes differentiated in culture. Testosterone-treated cells showed fewer and smaller lipid droplets than control cells and a dose-dependent inhibition of UCP1 mRNA expression, under adrenergic stimulation by norepinephrine (NE). These effects were reverted by the androgen receptor antagonist flutamide, suggesting they are dependent, at least in part, on the androgen receptor. Progesterone- and 17-β-estradiol-treated cells showed more and larger lipid droplets and progesterone stimulated NE-induced UCP1 mRNA expression at the lower concentration tested, but not at higher concentrations, suggesting that for brown adipocytes, this hormone is dose dependent. 17-β-Estradiol did not have any remarkable effect either on UCP1 or UCP2 mRNA expression. Interestingly, the specific progesterone receptor antagonist RU486 induced UCP1 and UCP2 mRNAs, including UCP1 mRNA expression in non-NE-treated brown adipocytes, suggesting a profound effect of this anti-progestagen on brown adipocyte thermogenic capacity. Thus, are conclude that testosterone, 17-β-estradiol, progesterone and RU486 have distinct actions on brown adipocytes, thus modulating UCP1 and UCP2 mRNA expression and/or lipid accumulation, and that sex hormones are factors that may explain in part the gender-dependent BAT thermogenic response. Received 24 June 2002; received after revision 20 August 2002; accepted 26 August 2002 RID="*" ID="*"Corresponding author.     

Influence of brown adipose tissue on deep cervical temperature during sleep in the young rabbit

Summary In young rabbits the slope of the temperature in the deep cervical region close to brown adipose tissue increased during desynchronized sleep at low ambient temperature. No increase occurred at neutral ambient temperature. In control rabbits (after disappearance of brown adipose tissue), the slope of deep cervical temperature did not increase during desynchronized sleep at low or neutral ambient temperatures.Preliminary data were reported at the Association des Physiologistes, Réunion de Poitiers, 20–23 June 1983.Acknowledgments. We wish to thank Giuseppe Mancinelli and Leonida Sabattini for technical assistance. This work was supported by a grant from the Consiglio Nazionale delle Ricerche, Rome. J.P.L. wishes to thank NATO for partial financial support during his stay at the Physiology Department in Bologna.     

Brown adipose tissue activity in hypophysectomized rats: involvement of sympathetic system

Summary At thermal neutrality, hypophysectomy enhanced interscapular brown adipose tissue (IBAT) activity (increase of purine nucleotide binding) in the rat. This stimulation is dependent on sympathetic system integrity since surgical denervation of IBAT imparis its thermogenic response.     

Effects of thyroidectomy and thyroxine replacement on the responsiveness of the anterior pituitaries from male rats to thyrotropin-releasing hormone in vitro

Summary Thyroidectomy decreased prolactin concentrations in the anterior pituitary (AP) and serum of the male rat. The amount of basal and thyrotropin-releasing hormone (TRH)-stimulated release of prolactin by AP in vitro was lower in thyroidectomized (Tx) rats than in sham Tx rats. These results suggest that the inhibitory effects of thyroidectomy on pituitary and serum prolactin in male rats are mediated in part by the reduction of the production and spontaneous release of prolactin and the responsiveness of prolactin to TRH.     

The effects of juvenile hormone analogues on the eggs ofPieris brassicae L.

Summary Mortality was produced in the eggs ofP. brassicae after treatment with 3 juvenile hormone analogues. The mortality was greatest in the early stages of embryonic development.I am grateful to the United Kingdom Ministry of Agriculture, Fisheries and Food, who provided a Research Studentship for this work.     

A new type of antiserum to thyrotropin-releasing hormone; detection of new TRH-immunoreactive cell groups in rat hypothalamus

Summary We produced a new type of antiserum to thyrotropin-releasing hormone (TRH) in rabbits. The immunogen is TRH-BSA, the production of which is based on the formation of an amide bond using carbodiimide (EDC). The specificity of the antiserum was assessed by enzyme immunoassay (EIA) and immunohistochemistry. When using the anti-TRH serum for immunohistochemistry in rat hypothalamus, new magnocellular groups were detected in the ventrolateral parts of the posterior hypothalamus and the dorsal parts of the third ventricle. Colchicine treatment was found not to be necessary to visualize perikarya containing TRH.     

Proinsulin C-peptide and its analogues induce intracellular Ca2+ increases in human renal tubular cells

Based on the findings that proinsulin C-peptide binds specifically to cell membranes, we investigated the effects of C-peptide and related molecules on the intracellular Ca²⁺ concentration ([Ca²⁺]_i) in human renal tubular cells using the indicator fura-2/AM. The results show that human C-peptide and its C-terminal pentapeptide (positions 27–31, EGSLQ), but not the des (27–31) C-peptide or randomly scrambled C-peptide, elicit a transient increase in [Ca²⁺]_i. Rat C-peptide and rat C-terminal pentapeptide also induce a [Ca²⁺]_i response in human tubular cells, while a human pentapeptide analogue with Ala at position 1 gives no [Ca²⁺]_i response, and those with Ala at positions 2–5 induce responses with different amplitudes. These results define a species cross-reactivity for C-peptide and demonstrate the importance of Glu at position 1 of the pentapeptide. Preincubation of cells with pertussis toxin abolishes the effect on [Ca²⁺]_i by both C-peptide and the pentapeptide. These results are compatible with previous data on C-peptide binding to cells and activation of Na⁺,K⁺ATPase. Combined, all data show that C-peptide is a bioactive peptide and suggest that it elicits changes in [Ca²⁺]_i via G-protein-coupled pathways, giving downstream enzyme effects. Received 13 May 2002; accepted 16 May 2002     

Enzymatic formation of potential anticancer and antiviral inosine analogues

Theoretically, inosine analogues should act as effective inhibitors of tumor cell proliferation and viral replication. To acquire a broad spectrum of new candidate inosine analogues, a rapid, facile, quantitative and stereoselective method for deaminating potential antitumor and antiviral adenine analogues previously synthesized in our laboratory was developed. A novel 5-adenylic acid deaminase, with relaxed substrate requirements, fromAspergillus species was utilized to deaminate four hexofuranosyladenine nucleosides and five adenine nucleoside dialdehydes to their corresponding inosine analogues. The fastest rates of deamination for the hexofuranosyl nucleosides were for the compounds where the vicinal hydroxyl groups on the sugars are oriented in the erythro configuration. For rapid deamination of the adenine nucleoside dialdehydes, theR configuration at the proximal carbon atom is preferred, while the nature of the group on the distal carbon atom has no significant effect on the rate or extent of deamination.     

Biological activity of synthetic moulting hormone analogues in the blowflyCalliphora stygia

Résumé L'activité biologique de la 2, 22, 25-trideoxy--ecdysone chezCalliphora est plus élevéc que celle de toutes les substances analogues examinées.     

Antagonism by thyrotropin-releasing hormone (TRH) of pentobarbital-induced hypothermia in rats with brain lesions

Summary Anesthesia with a large dose of pentobarbital (55 mg/kg, i.p.) caused a sustained decrease in brain temperature (Tb), which was monitored with a probe placed in the midbrain reticular formation. The administration of TRH to the lateral ventricle antagonized this hypothermia. None of the acute surgeries examined in this paper (adrenal-demedullectomy, septal knife cuts, electrolytic lesions of the hypothalamus and midbrain knife cuts) had any essential effect on this antagonism by TRH. These results suggest that centrally-administered TRH exerts its effect on thermoregulation, at least in part, through brain structure(s) caudal to the midbrain.     

Delayed effects of juvenile hormone analogues on metamorphosis ofPyrrhocoris apterus are not mediated by the corpus allatum

Summary While it is clear that juvenile hormone analogues disturb metamorphosis, there is some controversy about their effect on the activity of the corpus allatum in the course of metamorphosis. The present experiments showed that juvenile hormone analogues applied to eggs did not prevent inactivation of the corpus allatum at the onset of the last larval instar ofPyrrhocoris apterus.     

Effect of steviol and its structural analogues on glucose production and oxygen uptake in rat renal tubules

Summary The effect of several natural products ofStevia rebaudiana on glucose production and oxygen uptake in rat renal cortical tubules was investigated. Steviol, isosteviol and glucosilsteviol decreased glucose production and inhibited oxygen uptake. The sweet principle stevioside, and steviolbioside, however, were without effect on gluconeogenesis and oxygen uptake.     

Effect of steviol and its structural analogues on glucose production and oxygen uptake in rat renal tubules

The effect of several natural products of Stevia rebaudiana on glucose production and oxygen uptake in rat renal cortical tubules was investigated. Steviol, isosteviol and glucosilsteviol decreased glucose production and inhibited oxygen uptake. The sweet principle stevioside, and steviolbioside, however, were without effect on gluconeogenesis and oxygen uptake.     

The effects of vitamin E-deficiency on serum prolactin and serum luteinising hormone levels in the pregnant rat

Summary No significant differences were observed between the serum prolactin or serum LH levels of vitamin E-deficient or vitamin E-replete rats during the first 12 days of gestation. It is suggested that pituitary dysfunction is not the cause of the characteristic foetal resorption observed in vitamin E-deficient rats.Acknowledgments. The authors would like to thank Dr A.F. Parlow of the NIAMDD Rat Pituitary Hormone Distribution Programme for the generous supply of kits for the measurement of rat prolactin and LH, and Dr K.M.L. Morris (City of London Polytechnic) for arranging facilities for the radioiodination of the purified hormones used in the radioimmunoassays.     

Early effects of growth hormone on blood and urinary inorganic phosphorus in the rat (author's transl)]

From the kinetic study of the effects of one single growth hormone (GH) injection on the phosphate metabolism, it appears that the influence of GH on the serum phosphate level is biphasic: a decrease is followed by an increase. Conversely GH leads to an early decrease of the urinary phosphate excretion.     

A depolymerizing effect of the luteinizing hormone and follicle stimulating hormone on the neurotubules of the hypothalamus-hypophysial tract in the rat

Résumé Les neurotubules des fibres nerveuses du tract hypothalamo-hypophysaire du rat sont désorganisées après des traitments in vitro avec l'hormone lutéinisante et l'hormone folliculaire stimulante. Le méchanisme de dépolymérisation est discuté.