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ABSTRACT
In urethane-anaesthetized ovariectomized rats, injection of porcine relaxin (7·5 and 15 μg/kg, i.v.) caused a sustained increase in circulating plasma oxytocin and vasopressin concentrations; 10 μg relaxin/rat i.v. produced a smaller but significant increase in plasma oxytocin concentration in conscious ovariectomized rats. A significant increase in oxytocin concentration and inhibition of the spontaneous milk-ejection reflex was also seen in anaesthetized (ovary intact) lactating rats following injection of relaxin (7·5 μg/kg, i.v.). To investigate whether relaxin acts by increasing the electrical activity of oxytocin neurones or by facilitating stimulus-secretion coupling in the pituitary, the electrical activity of neurones in the supraoptic nucleus was recorded in urethane-anaesthetized lactating rats and in ovariectomized rats. Porcine relaxin (10 μg/rat, i.v.) increased the firing rate of both oxytocin and vasopressin neurones in the supraoptic nucleus in lactating rats. The response to relaxin was unaffected by subsequent injection of naloxone (1 mg/kg, i.v.). Oxytocin neurones were also activated by injection of relaxin (10 μg/rat) into ovariectomized rats. Combining the electrophysiological data, the neuronal activation following relaxin was significantly correlated with the level of spontaneous activity prior to relaxin injection. The results show that relaxin acts centrally to increase circulating plasma oxytocin and vasopressin concentrations by an opioid-independent mechanism.
Journal of Endocrinology (1992) 132, 149–158
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Search for other papers by O Doutrelant-Viltart in
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Abstract
In the rat, the synthetic GH secretagogue GH-releasing peptide (GHRP-6) acts centrally to activate a subpopulation of arcuate neurones as reflected by increased electrical activation and by the detection of Fos protein in cell nuclei. Since GHRP-6 also induces GH secretion via a direct action on the pituitary, we set out to determine whether the central actions of GHRP-6 are mediated by GH itself. First, we demonstrated that peripherally administered GHRP-6 induces Fos expression in the arcuate nucleus of GH-deficient animals (dw/dw rats and lit/lit mice). Secondly, in dw/dw rats, neither intracerebro-ventricular injection of 15 μg recombinant bovine GH nor 1 μg recombinant human IGF-I resulted in an increase in the number of cells expressing Fos protein in the arcuate nucleus (or in any other hypothalamic structure studied). These results support our hypothesis that GHRP-6 has a central site and mechanism of action and provide evidence to suggest that the activation of arcuate neurones by GHRP-6 is not mediated by a central action of GH or IGF-I. Furthermore, since the lit/lit mouse pituitary does not release GH following GHRP-6 administration, our finding that the central actions of GHRP-6 remain intact in these animals suggests the possible existence of two subpopulations of putative GHRP-6 receptors.
Journal of Endocrinology (1995) 146, 519–526
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ABSTRACT
We have previously demonstrated that retinoic acid (RA) as well as thyroid hormone stimulates GH gene expression. To clarify the relationship between the action of RA and thyroid hormone, pituitary-specific gene expression was investigated further in rat pituitary cells.
Rat clonal pituitary cells, GH3, were treated with RA with or without tri-iodothyronine (T3) for up to 3 days. After treatment with 10–1000 nmol RA/1 with or without 0·1–10 nmol T3/1, medium was collected for radioimmunoassay and cells were subjected to RNA extraction, and GH and prolactin gene expression was analysed using 32P-labelled rat GH and rat prolactin cDNA probes respectively. The data demonstrated the dose–responsive manner of the stimulatory effects of RA and T3 on GH secretion with T3-depleted media. The action of RA was additive to that of T3 for GH secretion when maximum effective doses of RA or T3 were used. Using dot blot and Northern gel analysis, it was shown that RA increased GH mRNA levels in T3-depleted media, and that this action of RA was additive to that of T3 on the induction of GH mRNA levels. In contrast, neither RA nor T3 stimulated the secretion of prolactin and prolactin mRNA levels in these cells.
Our results indicate that RA stimulates GH mRNA increment and GH secretion in T3-depleted media, and that the stimulatory effect of RA is additive to the maximum effective dose of T3.
Journal of Endocrinology (1990) 125, 251–256
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Search for other papers by T. Purdew in
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ABSTRACT
Plasma samples obtained at 4-h intervals from goats for at least 24 h before and then during 24 h of deprivation of water were analysed by radioimmunoassay for vasopressin and oxytocin concentrations. The samples were also analysed for osmolality and sodium concentration. The differential effect of night/day versus day/night deprivation was also studied. During the two periods before the two deprivations osmolality varied in a regular manner, with low values occurring at 08.00 h. Sodium concentration followed osmolality, whereas vasopressin did not vary during the period before deprivation. During deprivation vasopressin increased along with osmolality and sodium concentration, with the beginning of the increase occurring after the morning feed. Oxytocin levels did not increase during the period of deprivation.
These results do not support the hypothesis of general release of neurohypophysial hormones in response to osmotic stimuli but instead indicate there are species variations with respect to hormonal response to water deprivation.
J. Endocr. (1986) 110, 335–340
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Search for other papers by G Leng in
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Abstract
Previously, we demonstrated that the synthetic hexapeptide GH-releasing peptide (GHRP-6) activates a subpopulation of arcuate neurones, as reflected by increased electrical activation and by the detection of Fos protein in cell nuclei. Here we set out to determine (1) what proportion of the cells activated by GHRP-6 are neurosecretory neurones and (2) whether the cells activated by GHRP-6 contain tyrosine hydroxylase (TH; a marker of dopaminergic cells in this region) or β-endorphin. In the first study, adult male rats were injected i.v. with the retrograde tracer, Fluorogold, to detect cells which project outside the blood–brain barrier (and are therefore likely to be neurosecretory neurones). Three days later the conscious rats were injected i.v. with 50 μg GHRP-6 and the brains processed for the immunocytochemical detection of Fos protein. Between 68% and 82% of the arcuate neurones expressing Fos protein following GHRP-6 injection were retrogradely labelled with Fluorogold. In the second study, conscious male rats, bearing a chronically implanted jugular catheter, were killed 90 min following an i.v. injection of 50 μg GHRP-6 and the brains were processed for the double immunocytochemical detection of Fos protein and either TH or β-endorphin. Less than 7% (mean ± s.e.m.= 6·7 ± 2·6% nuclei/section per rat) of the arcuate neurones expressing Fos protein following GHRP-6 injection were TH-containing cells. Of 143β-endorphin-containing arcuate cells detected only four cells were identified as containing Fos protein. Thus, the majority of arcuate neurones activated by GHRP-6 (1) project outside the blood–brain barrier (and are therefore likely to be neurosecretory neurones) and (2) were not identified as TH- or β-endorphin-containing cells.
Journal of Endocrinology (1996) 151, 323–331
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Search for other papers by J. A. Russell in
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ABSTRACT
Pregnant rats were ovariectomized (or shamovariectomized) on days 17, 18 or 21 of pregnancy and oestradiol-17β and progesterone were replaced. Prepartum oxytocin concentrations were significantly lower in ovariectomized steroid-treated rats than in intact controls, and on day 21 of pregnancy injection of relaxin into acutely ovariectomized rats significantly increased plasma oxytocin concentrations. During parturition, injection of the opioid antagonist naloxone induced significant increases in plasma oxytocin concentration compared with salineinjected rats. The naloxone-induced increase was significantly less in ovariectomized steroid-treated rats than in rats with intact ovaries, indicating that endogenous opioid activity is less in ovariectomized rats than in intact rats. The progress of parturition in the ovariectomized steroid-treated rats was severely disrupted compared with sham-ovariectomized rats despite similar plasma oxytocin levels at the birth of pup number 2; this disruption was not overcome by injection of naloxone or by the consequent increase in oxytocin secretion, indicating deficient preparation of the uterus and birth canal in the absence of relaxin. We conclude that the decreased oxytocin concentrations prepartum, the prolongation of parturition and the decrease in opioid tone in ovariectomized steroid-treated rats may be partly due to a lack of relaxin produced by the ovary.
Journal of Endocrinology (1993) 138, 13–22
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Search for other papers by G Leng in
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Abstract
The physiological importance of oxytocin for the initiation and maintenance of labour and delivery is controversial. We investigated the effects of two novel peptide oxytocin antagonists on the onset and the progress of delivery in rats implanted with a jugular vein cannula one day before term. During delivery rats were given either an oxytocin antagonist (OVT16, n=10, or F382, n=7, 30 μg/kg) or vehicle (n=10, 9) after the birth of the second pup and the time to deliver five more pups was recorded. Other rats were given an injection of F382 (30 μg/kg, n=7) or vehicle (n=9) after the birth of the fourth pup and the time to deliver three more pups was recorded. In another experiment rats were given repeated injections of F382 (30 or 60 μg/kg, n=13, 11) or vehicle (n=32) prepartum on the day of expected term and the time of onset and the progress of delivery was recorded.
Rats given an antagonist after the second pup delivered the next five pups in 100 ± 8 min (F382) and 83 ± 12 min (OVT16), significantly slower than the respective controls (51 ± 6 and 49 ± 6 min, U-test, P<0·05). Four of the 7 rats given F382 after the fourth pup showed no prolongation of delivery (time between pups 4–7: 24·7±2·9 vs 27·5±3·1 min in controls), while in the other three rats delivery was prolonged (time between pups 4–7: 86 ± 4·3 min). The onset of delivery was significantly delayed in rats given repeated injections of F382 at 60 μg/kg on the afternoon of expected delivery but before labour had begun (median shift 14·5 h vs controls, U-test, P<0·05). These results suggest that in rats oxytocin is involved in both the initiation and the maintenance of parturition and that it is more important during the early rather than the later stages of delivery.
Journal of Endocrinology (1995) 145, 97–103
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ABSTRACT
Pregnant rats were implanted with subcutaneous minipumps to deliver either naloxone or saline. The time-course of subsequent parturition was different between the two groups: the interval between successive births was significantly shorter for the naloxone-treated rats. This supports the hypothesis that the opioid innervation of the neurohypophysis, which is known to influence oxytocin release profoundly, has a physiological role in parturition. To test the further hypothesis that this role is particularly important in a stressful environment, pregnant rats, again implanted with minipumps, were regularly transferred, at 15-min intervals beginning with the birth of the first pup, between their normal cage and the unfamiliar environment of a glass observation chamber. No difference was noted between the time-courses of parturition for the naloxone- and saline-treated groups, although the time-courses were markedly altered from those observed in rats not subjected to an unfamiliar environment. We conclude that opioid modulation of oxytocin release may play a role in 'spacing' the delivery of successive births during normal parturition.
J. Endocr. (1985) 106, 219–224
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ABSTRACT
Plasma samples were obtained before and during parturition from conscious rats implanted chronically with a jugular cannula. Rats were either allowed to remain in their nesting cage throughout parturition, or were moved immediately following the birth of the second or third pup into an empty glass chamber. The time-course of parturition was prolonged for mother rats which were moved in mid-parturition to this unfamiliar environment. However, in rats given an i.v. injection of the opioid antagonist naloxone at the time of transfer, parturition followed a normal time-course, and plasma oxytocin levels were significantly higher than in animals injected with saline. Thus our hypothesis is that stress activates opioid pathways which delay parturition by inhibiting oxytocin release. Opioid-mediated mechanisms may similarly be responsible for some problems in human parturition.
J. Endocr. (1987) 114, 247–252
