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SUMMARY
Pituitaries from Japanese quail were superfused continuously for up to 12 h and the luteinizing hormone (LH) in the superfusate was measured by radioimmunoassay. After an initial period the release rate remained low and relatively constant. The introduction of hypothalamic extracts prepared from quail substantially increased immunoreactive LH release. The responses were dose-dependent. Cortical extracts caused a minor but significant response. Dopamine was inactive in the system. The technique is attractive because it allows for repetitive stimulation of the same pituitary glands with treatments being administered every 30–45 min.
Search for other papers by OLIVE W. SMITH in
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SUMMARY
A Pettenkofer and sulphuric acid chromogen, excreted as a glucuronide and found in the fractions of urine that also contain hydroxylated Δ5-3β-hydroxysteroids and pregnanediol, was identified as p-menth-1-ene-8,9-diol (uroterpenol). Pettenkofer chromogenicity in a compound of this nature has not previously been reported. The recovery of uroterpenol in urine after ingestion of limonene showed that it was a metabolic product of this unhydroxylated monoterpene. Although experiments on its excretion by normal subjects indicated that it was largely, if not entirely, of dietary origin, there was evidence that its rate of excretion in women was influenced by endocrine factors. Hormonal effects on the formation and/or excretion of glucuronides in general are suggested. Care is needed to ensure that dietary constituents and their metabolites, which are excreted as glucuronides and exhibit colour reactions commonly used in the estimation of urinary steroids, are not confused with hormonal metabolites.
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Isolated porcine thyroid cells were surface-labelled with 125I using the lactoperoxidase technique. Samples of the cells were then cultured and harvested at various intervals for up to 7 days. The labelled proteins remaining on the cells or shed into the culture medium were analysed by electrophoresis on polyacrylamide gels run in sodium dodecyl sulphate. These studies indicated that the several different surface proteins of the thyroid cells were lost from the cell surface at similar rates (half-time of approximately 28 h) as the result, at least in part, of a process which depended on active cell metabolism. In addition, the gel profiles obtained from analysis of both medium and membrane-bound labelled proteins were similar and this suggested that peptide cleavage was not involved in the shedding of the majority of these proteins.
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Search for other papers by D M Smith in
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Abstract
We have investigated the effects of antisense oligodeoxynucleotides (oligos) to islet amyloid polypeptide (IAPP) mRNA on the expression and secretion of IAPP and insulin, in the clonal β-cell line HIT-T15. Phosphorothioate-modified oligos were cytotoxic compared with phosphodiester (D)-oligos. Of the nine oligos tested using a lipofection reagent, 03, a 30-mer D-oligo complementary to a sequence downstream of the IAPP initiation codon, showed a significant dose-dependent suppression of IAPP mRNA, with a 42% decrease at 7·5 μm, compared with a scrambled (MS03) control oligo (n=3, P<0·01). A subsequent 89% suppression of IAPP release was observed in the 4-h period following antisense treatment (1·78 ± 0·13 (MS03) vs 0·19 ± 0·14 (03) pmol/106 cells per 240 min, n=7, P<0·01). A significant increase in insulin mRNA (100 ± 10% (MS03) vs 124 ± 8% (03), n=3, P<0·05) and insulin content (13·0 ± 0·9 (MS03) vs 17·4 ± 1·4 (03) pmol/106 cells, n=7, P=0·028) was observed following treatment with 03 at 7·5 μm. 08, a 20-mer D-oligo directed to a region of IAPP mRNA further downstream than 03, also showed a decrease in IAPP mRNA and peptide release and an increase in insulin content. No significant changes were observed in the expression and release of the unrelated β-cell peptide, neuropeptide Y. We thus show a suppression of synthesis and release of IAPP in HIT-T15 cells using antisense oligos. The associated increase in insulin mRNA and content in these cells after treatment with IAPP antisense oligos is in accord with an inhibitor action of IAPP on insulin availability.
Journal of Endocrinology (1996) 151, 341–348
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Search for other papers by C. P. Smith in
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Search for other papers by M. L. Forsling in
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ABSTRACT
The contribution of oxytocin to the maintenance of renal Na+ excretion in the Brattleboro rat has been examined in animals infused with hypotonic saline. Brattleboro rats exhibited hypernatraemia and hyperosmolality associated with greatly increased plasma concentrations of oxytocin by comparison with Long–Evans control rats. Neurohypophysectomy to remove the secretion of the remaining posterior pituitary peptide, oxytocin, led to greatly diminished rates of Na+ excretion in the Brattleboro rat. Oxytocin replacement to achieve plasma levels equivalent to those in intact Brattleboro rats produced a substantial and sustained natriuresis in the neurohypophysectomized animal. Oxytocin secretion evoked in response to saline infusion would thus appear to be effective in promoting renal Na+ excretion in the absence of vasopressin in the Brattleboro rat.
Journal of Endocrinology (1991) 129, 49–54
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Search for other papers by R L Smith in
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Abstract
IGF-I is the major anabolic factor for cartilage matrix production. Chondrocytes and cartilage treated with interleukin-1α (IL-1α), and chondrocytes from several models of inflammatory joint disease, exhibit reduced responsiveness to IGF-I. Since the IGF-binding proteins (IGFBPs) modulate the effects of IGF-I, we examined the effect of IL-1α and tumor necrosis factor-α (TNF-α) on IGFBP production by normal human articular chondrocytes in primary culture. Western ligand blots and immunoprecipitation of conditioned medium samples showed that articular chondrocytes produced IGFBPs-2, −3 and −4 and glycosylated IGFBP-4. Both IL-1α and TNF-α increased chondrocyte production of IGFBP-3, but did not alter IGFBP-4 production. The activity of a neutral metalloprotease with the ability to cleave IGFBP-3 was also increased by IL-1α. These data suggest that the cytokines IL-1α and TNF-α may act to reduce IGF-I access to chondrocytes by increasing production of IGFBP-3. This may be a factor in the decreased matrix production in the inflammatory arthritides.
Journal of Endocrinology (1995) 146, 279–286
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Search for other papers by S. SMITH in
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A method of estimating thyroid function with carrier-free radio-iodine which provides an arbitrary numerical scale of thyroid activity is described. It is suitable for investigating borderline thyroid dysfunction.
The results on over 500 psychiatric patients are given in the form of histograms, and arbitrary limits of normality are defined on the basis of these results.
While there is usually a correlation between the tracer method and the basal metabolic rate, cases exist in which increased thyroid activity, determined by the radio-active method, is associated with normal or subnormal b.m.r. and vice versa. This is explained as a disturbance of the sensitivity of body tissues to thyroid hormone.
The significance of under-sensitivity to thyroid hormone and related problems is discussed, and the importance of considering peripheral sensitivity of the tissues of the body in evaluating an abnormal thyroid activity is emphasized.
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ABSTRACT
A study was performed investigating the daily patterns of hormone release accompanying changes in fluid balance in the male rat during 48 h of dehydration. The blood volume decreased by 18%, the largest change occurring during the initial period when the rats showed an effective loss of body sodium. During the second day of dehydration, sodium retention was again seen. Plasma sodium concentrations showed a progressive increase, the total rise being 5–6%; the greatest changes were seen during the dark phases of the cycle which may be due to the nocturnal food intake.
Plasma vasopressin and oxytocin concentrations were significantly elevated throughout dehydration to levels which could be reproduced by acutely increasing plasma sodium and decreasing blood volume to the same extent. The observed increases were influenced by the phase of the day–night cycle, being greatest over the dark phases of the cycle. The overall increases were greatest when dehydration commenced at the start of the dark phase. Dehydration initially led to a rise in plasma corticosterone concentrations, whilst plasma concentrations of atrial natriuretic peptide were decreased. Plasma angiotensin II concentrations rose significantly during the later period of sodium retention.
Journal of Endocrinology (1993) 137, 311–319
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ABSTRACT
Quantitative in-vitro receptor autoradiography has been used to localize and compare the anatomical distribution of binding sites for iodinated endothelins (ET-1, ET-2 and ET-3) in human uterus. Binding sites for the three iodinated isoforms had a similar gross anatomical distribution. The density of binding sites was significantly higher in the endometrium compared with the myometrium and greatest at the endometrial–myometrial junction.
In cross-competition experiments, unlabelled ET-1, ET-2, ET-3, sarafotoxin S6b and mouse vasoactive intestinal contractor (1 μmol/l) competed for the binding sites of all the iodinated peptides suggesting that ETs may bind to the same receptor. However, preproendothelin(110–130) (endothelin-like peptide) or preproendothelin(124–130) and other non-endothelin vasoactive peptides tested as a concentration of 1 μmol/l did not compete.
Micro-autoradiography revealed that high densities of iodinated ET-1, ET-2 and ET-3 binding sites were localized to glandular epithelial cells and blood vessels with lower levels in the myometrium and vascular smooth muscle, suggesting that these potent vasoactive and proliferative agents could play a role in the control of menstruation.
Journal of Endocrinology (1991) 129, 149–154
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Unit of Experimental Therapeutics, Institute of Cancer Sciences, University of Glasgow Glasgow, UK
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Institute for Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa
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Kisspeptin signalling is indispensable for fertility, stimulating gonadotropin-releasing hormone (GnRH) secretion and mediating gonadal steroid feedback on GnRH neurons. Moreover, kisspeptin neurons have been implicated in other non-reproductive neuroendocrine roles. Kisspeptin appears to also regulate growth hormone secretion but much of the data appear contradictory. We sought to clarify a potential role of kisspeptin in growth hormone (GH) regulation by examining the effect of kisspeptin antagonists on GH secretion in ewes under various physiological conditions. Our data show clear and robust increases in GH secretion following lateral ventricle or third ventricle infusion of kisspeptin antagonists p-234 and p-271 in either ovariectomized or anestrous ewes. Central infusion of kisspeptin-10 had no effect on GH secretion. To determine the level at which kisspeptin may influence GH secretion, we examined expression of the cognate kisspeptin receptor, GPR54, in pituitary cells and showed by immunocytochemistry that the majority of somatotropes express GPR54 while expression was largely negative in other pituitary cells. Overall, we have demonstrated that blocking kisspeptin signalling by antagonists stimulates GH secretion in ewes and that this is likely mediated by inhibiting endogenous kisspeptin activation of GPR54 expressed on somatotropes. The findings suggest that endogenous kisspeptin inhibits GH secretion through GPR54 expressed on somatotropes.
