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Search for other papers by S. W. C. CHAN in
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Search for other papers by I. P. CALLARD in
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SUMMARY
The synthesis of steroids from [7α-3H]cholesterol, [7α-3H]pregnenolone and [7α-3H]progesterone by lizard and turtle ovarian tissues in vitro was studied. Progesterone, 17α-hydroxyprogesterone, dehydroepiandrosterone, androstenedione, testosterone, oestrone and oestradiol were identified as products. In the turtle (Pseudemys), conversion of pregnenolone to progesterone was efficient, but transformation of progesterone to other steroids was relatively slow as indicated by the accumulation of progesterone over the incubation period. In Dipsosaurus, accumulation of radioactivity was greatest in testosterone, the quantities of which continued to increase at each sampling period. The rate of utilization of pregnenolone as a substrate was similar for the two species studied and the quantities of oestrone and oestradiol formed were lower in Pseudemys. The use of progesterone as precursor by Dipsosaurus ovarian tissue revealed a similar pattern of Δ4-steroid metabolism to that obtained with pregnenolone as precursor.
The effects of addition of purified follicle-stimulating hormone (FSH) and luteinizing hormone (LH) on the metabolism of [14C]cholesterol in vitro was studied using Pseudemys follicular tissue. The pattern of cholesterol metabolism was similar to that for pregnenolone in this species. The synthesis of pregnenolone, progesterone, dehydroepiandrosterone and androstenedione in vitro was significantly enhanced in the presence of LH. Follicle-stimulating hormone had no effect on steroid synthesis except for a decrease of androstenedione formation. The stimulatory effect of LH on steroidogenesis in vitro is discussed in relation to the literature suggesting that mammalian FSH, but not LH, stimulates all phases of reptilian ovarian function when injected in vivo.
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Search for other papers by J. G. PHILLIPS in
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SUMMARY
Cyclical changes in the activity of adrenocortical tissue are a wellestablished phenomenon in many amphibian species but up to now they have been studied by observing changes in cytology or enzyme activity, e.g. steroid-3β-ol dehydrogenase. The present study was designed to provide a measure of corticosteroid secretion throughout the seasons using the in-vitro approach. Concomitant histological changes are also recorded and together provide evidence that the adrenal tissue of Rana rugulosa shows maximum activity in the spring spawning season and reaches a minimum in winter.
Search for other papers by W Zhao in
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Search for other papers by P Y Leung in
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Search for other papers by S B Cheng Chew in
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Search for other papers by H C Chan in
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Search for other papers by P Y D Wong in
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Abstract
The localization and distribution of angiotensin II (Ang II) in the rat epididymis was studied using immunohistochemical and RIA techniques. The immunohistochemical results showed that Ang II-like immunoreactivity progressively increased along the length of the rat epididymis (cauda>corpus>>caput) and was predominately localized in the basal region of the epididymal epithelium. Occasionally, immunostaining of lighter intensity was also found in the apical region. The concentration of Ang II in cultured rat cauda epididymal epithelial cells was further measured by RIA. In addition to that found in cultured epithelial cells, Ang II activity was also detected in the culture medium, suggesting a secretory role of the epithelium. These findings suggest that Ang II could be derived locally from epididymal epithelium and that it could play a role in local regulation of epithelial transport and, possibly, in the maintenance of sperm function as well, by exerting its paracrine and/or autocrine effect in various regions of the epididymis.
Journal of Endocrinology (1996) 149, 217–222
Search for other papers by I. CHESTER JONES in
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Search for other papers by I. W. HENDERSON in
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Search for other papers by D. K. O. CHAN in
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Search for other papers by J. C. RANKIN in
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Search for other papers by J. I. S. ROBERTSON in
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Search for other papers by M. TREE in
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SUMMARY
Extracts of corpuscles of Stannius from the silver eel have been shown to contain a substance with a powerful pressor action on intravenous injection into the rat. This material resembles mammalian renin in being non-diffusible through cellophane, heat-labile, and destroyed by acidification to pH 2. The effect in the rat differs, however, from that produced by mammalian renin in being more prolonged, and frequently biphasic.
Pressor activity has also been demonstrated in extracts of kidneys from freshwater silver eels. Incubation of kidney extract with mammalian renin-substrate produced an angiotensin-like pressor substance.
Both renal and corpuscular extracts had a prolonged pressor effect on intravenous injection into the eel. The identities of these pressor materials have not been finally established.
Removal of the corpuscles of Stannius from freshwater silver eels was followed by a drop in blood pressure to levels normally found in eels adapted to seawater.
The possible existence, in the eel, of a renin-angiotensin system analogous to that existing in mammals is discussed.
Search for other papers by R J Lacey in
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Search for other papers by S L F Chan in
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Search for other papers by H C Cable in
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Search for other papers by R F L James in
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Search for other papers by C W Perret in
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Search for other papers by N G Morgan in
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Abstract
Sequences from cDNA molecules encoding α2-adrenoceptor subtype genes were subcloned into prokaryotic vectors and riboprobes generated to hybridise selectively with each of the human α2C2-, α2C4- and α2C10-adrenoceptor subtype mRNA species. The riboprobes were labelled with either 32P or digoxigenin and used to study the expression of α2-adrenoceptor subtypes in sections of human pancreas, in isolated human islets of Langerhans and in clonal HIT-T15 pancreatic β-cells. Using a ribonuclease protection assay protocol, expression of mRNA species encoding both α2C2 and α2C10 was demonstrated in preparations of isolated human islets of Langerhans. mRNA encoding α2C4 was also detected in human islet RNA, using reverse transcription coupled with the polymerase chain reaction. In situ hybridisation was then employed to examine the distribution of each α2-adrenoceptor subtype in sections of human pancreas. All three subtypes of α2-adrenoceptor mRNA were identified in sections of formalin-fixed, paraffinembedded human pancreas using riboprobes labelled with digoxigenin. Although some labelling of the three α2-adrenoceptor mRNA subtypes was seen in the islets, the labelling was most intense in the exocrine tissue of the pancreas for each receptor subtype. The specificity of the digoxigenin-labelled RNA probes was confirmed in several control tissues and by in situ hybridisation studies using sense probes in the pancreas. The integrity of the pancreas sections was confirmed by in situ hybridisation with an antisense riboprobe derived from human insulin cDNA. The results demonstrate that multiple α2-adrenoceptor subtypes are expressed in human pancreas. Both the exocrine and endocrine cells express more than one receptor subtype, although the islets stain less intensely than the bulk of the tissue suggesting that the islet cells may have lower levels of expression than the acinar tissue. The presence of α2-adrenoceptor subtype mRNA species in pancreatic β-cells was confirmed by Northern blotting of RNA extracted from the clonal β-cell line, HIT-T15. Transcripts encoding each of the three cloned α2-adrenoceptor subtypes were detected in HIT-T15 cells.
Hybridisation of sections of human pancreas with oligodeoxynucleotide probes designed to hybridise with β2-adrenoceptor mRNA revealed expression of this species in islet β-cells but not in the exocrine tissue of the pancreas.
Journal of Endocrinology (1996) 148, 531–543
Departments of Medicine and Physiology, University of Toronto, 1 Kings College Circle, Toronto, Ontario, M5F 1A8 Canada
Search for other papers by T S McQuaid in
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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
Search for other papers by C B Chan in
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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.
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Search for other papers by The Sanger Mouse Genetics Project in
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Search for other papers by A J L Clark in
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Search for other papers by L F Chan in
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Melanocortin receptor accessory protein 2 (MRAP2) is a transmembrane accessory protein predominantly expressed in the brain. Both global and brain-specific deletion of Mrap2 in mice results in severe obesity. Loss-of-function MRAP2 mutations have also been associated with obesity in humans. Although MRAP2 has been shown to interact with MC4R, a G protein-coupled receptor with an established role in energy homeostasis, appetite regulation and lipid metabolism, the mechanisms through which loss of MRAP2 causes obesity remains uncertain. In this study, we used two independently derived lines of Mrap2 deficient mice (Mrap2 tm1a/tm1a ) to further study the role of Mrap2 in the regulation of energy balance and peripheral lipid metabolism. Mrap2 tm1a/tm1a mice have a significant increase in body weight, with increased fat and lean mass, but without detectable changes in food intake or energy expenditure. Transcriptomic analysis showed significantly decreased expression of Sim1, Trh, Oxt and Crh within the hypothalamic paraventricular nucleus of Mrap2 tm1a/tm1a mice. Circulating levels of both high-density lipoprotein and low-density lipoprotein were significantly increased in Mrap2 deficient mice. Taken together, these data corroborate the role of MRAP2 in metabolic regulation and indicate that, at least in part, this may be due to defective central melanocortin signalling.
