Biomedical subjects

S L Lightman

Publications and source records attributed to S L Lightman.

At least 343 records · Page 19Linked to original sources

PubMed1988

Induction of luteal regression in the marmoset monkey (Callithrix jacchus) by a gonadotrophin-releasing hormone antagonist and the effects on subsequent follicular development.

Doses of 100 or 200 micrograms of a novel GnRH antagonist ([N-acetyl-D beta Na11-D-pCl-Phe2-D-Phe3-D-Arg6-Phe7-Arg8-D-Ala10]NH2 GnRH) (4 animals/dose) were administered on Days 10/11 of the luteal phase and induced a marked suppression of circulating bioactive LH and progesterone concentrations within 1 day of treatment (P less than 0.01). Thereafter, progesterone concentrations remained low or undetectable until after the next ovulation. Similar results were obtained when 200 micrograms antagonist were given on Days 5/6 of the luteal phase (N = 4). The interval from injection of antagonist (200 micrograms but not 100 micrograms) to ovulation (based on a rise in progesterone above 10 ng/ml) was significantly longer than that from prostaglandin-induced luteal regression to ovulation in control cycles (N = 4/treatment) (range, 13-15 days after antagonist vs 8-10 days after prostaglandin, P less than 0.01). This delay of 4-5 days was equivalent to the duration for which LH concentrations were significantly suppressed by 200 micrograms antagonist when administered to ovariectomized animals (N = 3). Corpus luteum function during the cycle after GnRH antagonist treatment appeared normal according to the pattern of circulating progesterone. These results show that corpus luteum function and preovulatory follicular development in the marmoset monkey are dependent on pituitary gonadotrophin secretion.

Animals↗

PubMed1988

Quantitative in-situ hybridization histochemistry studies on growth hormone (GH) gene expression in acromegalic somatotrophs: effects of somatostatin, GH-releasing factor and cortisol.

We have examined the effects of human GH-releasing factor (1-44) (GRF), cortisol and somatostatin-(1-14) on GH gene expression in solid tissue and dispersed cells from human pituitary adenomas using quantitative in-situ hybridization histochemistry. Sections cut from tissue obtained at hypophysectomy from three acromegalic patients were hybridized to probes directed against mature alpha-subunit, GH, prolactin, pro-opiomelanocortin, TSH beta-subunit and LH beta-subunit mRNA. Only one biopsy contained GH mRNA in isolation. A second was found to coexhibit GH, prolactin and alpha-subunit mRNA, and a third was found to contain prolactin, TSH beta-subunit, alpha-subunit and LH beta-subunit mRNA, with GH mRNA below the limit of specific detection, indicating that the sample was composed of normal rather than adenomatous pituitary tissue. GH mRNA in individual dispersed cells derived from the latter declined to barely detectable levels over 287 h, both in cultures containing GRF (10 ng/ml) or GRF (10 ng/ml) plus somatostatin (10 ng/ml) and in controls, but increased fourfold in cultures containing GRF (10 ng/ml) plus cortisol (0.5 mumol/l). GH mRNA remained unchanged in both adenoma samples over 138 and 450 h, irrespective of the addition of GRF or GRF plus hydrocortisone. In these samples, somatostatin plus GRF had no consistent effect. These studies confirm that quantitative in-situ hybridization histochemistry can be used to investigate hormone gene regulation in small samples of human tissue and should enable us to define more clearly the level at which abnormal gene regulation occurs.

Acromegaly↗

PubMed1988

Potentiation of lactation-induced oxytocin secretion by intracerebroventricular oxytocin in the conscious goat.

The release of oxytocin into the cerebrospinal fluid (CSF) and plasma of lactating goats was studied following implantation of cisternal and lateral ventricular cannulae. Hand milking was associated with a significant increase in plasma concentrations of oxytocin, but no change in plasma concentrations of vasopressin or CSF concentrations of oxytocin. Intracerebroventricular (i.c.v.) infusion of oxytocin itself (1 pmol/min for 60 min) had no effect on basal plasma levels of oxytocin. It did, however, markedly potentiate the milking-induced increase in plasma oxytocin above the levels achieved during i.c.v. infusion of artificial CSF alone. In the goat, therefore, milking results in a selective release of oxytocin into the plasma, and this release can be potentiated by the presence of increased concentrations of oxytocin in the CSF.

Animals↗

PubMed1988

Immunoreactive vasopressin and oxytocin in hypothalamo-hypophysial portal blood of the Brattleboro and Long-Evans rat: effect of adrenalectomy and dexamethasone.

Immunoreactive vasopressin and oxytocin were measured in the hypothalamo-hypophysial portal blood of both Long-Evans and homozygous Brattleboro rats. Adrenalectomy caused an increase in vasopressin immunoreactivity in portal blood in the Long-Evans strain, whilst administration of dexamethasone to these adrenalectomized animals resulted in a reduction in portal vasopressin immunoreactivity to levels below those seen in sham-operated animals. This vasopressin immunoreactivity co-eluted with synthetic vasopressin on high-pressure liquid chromatography (HPLC), and diluted in parallel in radio-immunoassay. In Brattleboro rats, however, although vasopressin-like immunoreactivity was detected, the portal concentration did not vary with the adrenal status of the animal, nor did it show the characteristics of standard vasopressin on HPLC or in immunoassay. Oxytocin was present in the portal blood of both Long-Evans and Brattleboro rats at similar very high concentrations, but did not vary in response to adrenalectomy. These results are consistent with a role for vasopressin, but not oxytocin, in the hypothalamic response to adrenalectomy and glucocorticoid feedback. Neither vasopressin immunoreactivity nor oxytocin appear to subserve this role in the homozygous Brattleboro rat.

Adrenalectomy↗

PubMed1988

Quantitative in-situ hybridization histochemistry in the rat pituitary gland: effect of bromocriptine on prolactin and pro-opiomelanocortin gene expression.

The temporal effect of orally administered bromocriptine on pro-opiomelanocortin (POMC) and prolactin gene expression in male Sprague-Dawley rats was examined using in-situ hybridization histochemistry. Messenger RNA in the anterior and intermediate lobes could be clearly delineated in each section. Administration of bromocriptine resulted in a reduction in hybridization of 35S-labelled cDNA probe to prolactin mRNA from 0.69 x 10(12) to 0.29 x 10(12) copies bound/g after 150 h. POMC mRNA in the anterior lobe remained unchanged with 0.08 x 10(12) copies of probe bound/g for the duration of the experiment, while in the intermediate lobe it decreased from 2.44 x 10(12) to 0.44 x 10(12) copies of probe bound/g at 150 h. The rate of reduction in intermediate lobe POMC mRNA was similar to that of prolactin mRNA for the first 24 h but was subsequently more rapid and more profound, falling to 20% of the control value at 84 h and to 18% at 150 h.

Animals↗

PubMed1988

Effects of beta endorphin on specific immune responses in man.

Synthetic human beta endorphin shows a biphasic effect on the production of specific anti-herpes viral antibodies in vitro. At higher concentrations antibody production is reduced, at lower concentrations it is enhanced. In a proportion of donors whose cells do not produce specific antibody when cultured with antigen alone, the lower concentrations of beta endorphin allow antigen-driven specific antibody production to occur. Specific anti-herpes viral antibodies are also made by natural killer (NK) cell-depleted populations from the same non-producer donors. beta endorphin also exerts biphasic effects on NK, although the direction of the modulation is a mirror image of the effects on antibody production. This suggests that the immunomodulatory actions of beta endorphin on specific immune responses are mediated in part by effects on NK suppressor-inducer cells.

Antibodies, Viral↗

PubMed1988

Therapy of advanced ovarian cancer with D-Trp-6-LH-RH (decapeptyl) microcapsules.

Forty-one patients with advanced ovarian cancer (FIGO stage III or IV) who had relapsed following conventional treatment were treated with long acting depot preparation of D-Trp-6-LH-RH once a month. There were no exclusion criteria and patients of any age or performance status were eligible. Thirty patients continued to progress following therapy. Twenty-six patients died within the first 16 weeks from onset of therapy. Five patients remained stable (SD) on D-Trp-6-LH-RH with no change in tumor size. Six patients had evidence of clinical and/or radiological partial remission (PR) where the tumor size decreased by more than 50%. The remissions in the responding patients were maintained for a mean duration of 10 months (range 6-18 months). Thus 11 patients (6 PR + 5 SD) have had remission or stabilization of disease which has been clinically worthwhile. Clinical benefit of therapy with microcapsules of slow-release D-Trp-6-LH-RH in about 26% of patients is highly encouraging. Treatment with D-Trp-6-LH-RH offers an important non-toxic alternative in patients who do not tolerate chemotherapy or who have progressive disease following chemotherapy.

Adult↗

PubMed1987

A role for the area postrema in mediating cholecystokinin-stimulated oxytocin secretion.

We have investigated the role of the area postrema (AP) in mediating the neurohypophyseal hormone response to peripheral administration of nausea-producing agents in rats. In control animals, lithium chloride (LiCl) and apomorphine (APO) caused a rise in plasma levels of immunoreactive oxytocin (OT) and arginine-vasopressin (AVP), whereas sulphated cholecystokinin octapeptide (CCK-8s) stimulated OT secretion only. Rats with AP lesions exhibited a similar OT and AVP response to LiCl and APO but the OT response to CCK-8s was significantly diminished. The results indicate that the selective stimulation of OT secretion by CCK-8s is partly mediated via the AP. Although the nausea-producing effects of LiCl and APO may involve the AP, the neuroendocrine effects of these agents may well be mediated via actions outside the AP.

Animals↗

PubMed1987

Temporal changes in the activity of endogenous opioid mechanisms regulating oxytocin secretion in saline-loaded rats.

The effect of the opiate antagonist naloxone on neurohypophyseal hormone secretion has been investigated in rats given 2% NaCl to drink for 0-9 days. Naloxone elicited a rise in plasma levels of oxytocin (OT), but not arginine-vasopressin (AVP), on days 1-3 only, the greatest response being on day 2. In a further experiment, the OT response to an acute stimulus (1.5 M NaCl, i.p.) was found to be similar in controls and rats drinking 2% NaCl for 7 days, indicating that depletion of readily releasable hormone was not the cause of the loss of sensitivity to naloxone; rather a down-regulation of opiate receptor mechanisms may be responsible. The temporal changes in opiate antagonist-sensitivity in saline-loaded rats may provide a functional paradigm for the investigation of regulatory opiate mechanisms in neural tissue.

Animals↗

PubMed1987

Intracerebroventricular arginine vasopressin causes intracranial pressure to rise in conscious goats.

The effects of intracerebroventricular (i.c.v.) infusion of arginine vasopressin (AVP) on intracranial pressure (ICP), blood pressure (BP) and plasma AVP were investigated in conscious goats. The animals were implanted with ventricular (V) and cisternal (C) cannulae under halothane anaesthesia and allowed to recover prior to experimentation. After 30 min infusion of 20 microliter/min artificial cerebrospinal fluid (CSF) alone, to allow the animals to settle, ICP (estimated at both C and V cannulae), BP and plasma AVP were measured. Then the animals were infused with either artificial CSF alone or 1 or 10 pmol/min AVP for a further 150 min. One pmol/min AVP i.c.v. resulted in significant ICP increases of +2.2 cm CSF (C) and +3.1 cm CSF (V) when compared with artificial CSF alone. Ten pmol/min AVP also led to significant ICP rises of +3.2 cm CSF (C) and +4.2 cm CSF (V). There were no significant changes of BP or plasma AVP during the infusions. We conclude that central infusion of AVP leads to elevated ICP in conscious goats by a mechanism that does not involve BP alteration or changes in plasma AVP.

Animals↗

PubMed1987

Evidence for a functional relationship between noradrenaline and neurohypophyseal peptides in the brainstem of rats.

The possibility of a functional relationship between noradrenaline and neurohypophyseal peptides in the control of cardiovascular function in the nucleus tractus solitarius of rats has been investigated. The hypotensive response to microinjections of noradrenaline (20 nmol) was abolished by simultaneous (but not prior) microinjections of [Arg8]vasopressin (AVP) and oxytocin at doses (0.9 pmol) which alone had no effects on cardiovascular parameters. AVP plus noradrenaline actually resulted in a transient pressor effect. Simultaneous administration of [deamino-D-Arg8]vasopressin, a selective agonist of AVP V2 receptors, did not modify the effect of noradrenaline, whereas the specific V1 antagonist D-(CH2)5-Tyr(Me)-AVP partially decreased its intensity. When subthreshold doses of both AVP (0.9 pmol) and noradrenaline (10 pmol) were administered simultaneously, a pressor response was observed. In vasopressin-deficient Brattleboro rats, microinjections of 0.9 pmol AVP had no effects, but a marked pressor response was observed after the administration of a higher dose (9 pmol). In parent strain Long-Evans rats, noradrenaline (20 nmol) also produced a hypotensive response, but in Brattleboro rats microinjections of this amine elicited a marked pressor effect. In these rats, simultaneous administration of a subthreshold dose of AVP (0.9 pmol) reversed this response in such a way that a fall in blood pressure, similar to that observed in Long-Evans rats after injection of noradrenaline alone, was registered. These results provide evidence for a functional interaction between noradrenaline and neurohypophyseal peptides in the control of cardiovascular function in the brainstem.

Animals↗

PubMed1987

Neurotensin in hypothalamo-hypophyseal portal blood.

The control of hypothalamo-hypophyseal neurotensin secretion was studied using a modification of the Worthington-Fink portal sampling technique. Portal concentrations of neurotensin were significantly greater than the concentrations found in peripheral plasma, and HPLC characterisation demonstrated that both portal and peripheral plasma neurotensin were very similar. Two different anaesthetic agents, urethane and althesin, did not differ in the resulting portal concentrations of neurotensin. Electrical stimulation of the median eminence resulted in a very marked increase in portal neurotensin concentration.

Animals↗

PubMed1987

Oxytocin in the central nervous system and sexual behaviour in male rats.

Concentrations of oxytocin (OT) and vasopressin (AVP) were measured in cerebrospinal fluid (CSF) obtained from the cisterna magna of freely moving rats. Basal levels of OT and AVP were approximately 9 fmol/ml in both male and female. In the male rats this increased to approximately 18 fmol/ml 5 min after ejaculation, and 27 fmol/ml 20 min after ejaculation. No increase from basal levels occurred when males were placed with unreceptive females, or alone in the test environment. AVP levels were unchanged in any condition. Preliminary investigations indicate that discrete electrolytic lesions to the lateral and posterior parvocellular hypothalamic paraventricular nucleus (PVN) abolished this ejaculation-associated increase in CSF OT, prolonged mount and intromission latencies and reduced the absolute postejaculatory interval (PEI). We conclude that intracerebrally projecting OT systems may be activated during coitus and may contribute to the mechanisms underlying postejaculatory refractoriness.

Animals↗

PubMed1987

Myxoedema presenting with chiasmal compression: resolution after thyroxine replacement.

A 60-year-old woman presented with deteriorating vision. A computed tomography (CT) scan showed pituitary enlargement with chiasmal compression. Serum prolactin levels were normal but assessment of thyroid function showed a serum thyroxine level of 25 nmol/l (normal range 76-160 nmol/l) and a thyroid-stimulating hormone (TSH) level of 60 mU/l (normal range 0.5-5.0 mU/l). After 8 weeks of thyroxine replacement therapy (0.05 mg daily increasing to 0.1 mg daily after 3 weeks) the visual defects had resolved, serum TSH had fallen to 0.7 mU/l, and the CT scan showed pronounced reduction in the size of the pituitary gland. Measurement of TSH as well as prolactin is essential in all patients with pituitary enlargement, to avoid unnecessary pituitary surgery.

Female↗

PubMed1987

Opioid control of oxytocin secretion: evidence of distinct regulatory actions of two opiate receptor types.

Stress induced oxytocin (OT) secretion was measured in female rats following treatment with various opiate antagonists selective for different types of opiate receptor. Naloxone (mu selective) and MR2266 BS (kappa selective) potentiated the OT response to an emotional stress (1 min. immobilization) whereas the delta selective antagonist ICI 154129 was without effect. Similarly, naloxone and MR2266 BS, but not ICI 154129, potentiated the response to a physical stress (i.p. hypertonic saline). A dose response comparison of the actions of naloxone and MR2266 BS revealed that naloxone was most effective in potentiating the immobilization response whereas MR2266 BS elicited greater responses than naloxone when administered prior to hypertonic saline. The results indicate that the opioid regulation of stress induced OT secretion is primarily mediated via mu and kappa opiate receptor types, the two types differentially regulating the OT response to two different stressors.

Animals↗

PubMed1987

Modulation of oxytocin secretion by ascending noradrenergic pathways: sexual dimorphism in rats.

We have investigated the role of ascending noradrenergic pathways in the control of oxytocin (OT) and arginine-vasopressin (AVP) secretion during acute immobilization stress in male and female rats. 6-Hydroxydopamine-induced lesions of the ventral noradrenergic bundle (VNAB) resulted in a selective depletion of hypothalamic noradrenaline content. In sham-lesioned rats plasma levels of OT were raised following stress, the response being significantly greater in female compared with male animals. VNAB lesions were not associated with altered responses in female rats, whereas lesioned males exhibited markedly elevated OT stress responses. AVP secretion was not modulated in VNAB-lesioned rats of either sex. The results provide functional evidence of a sexually dimorphic inhibitory role of the VNAB in the control of OT secretion.

Afferent Pathways↗

PubMed1987

Neuropeptide Y alters monoamine turnover in the rat brain.

The effects of intracerebroventricular administration of neuropeptide Y (NPY) on central monoamine turnover were studied in rats treated with alpha-methyl-p-tyrosine (alpha-MPT). NPY decreased noradrenaline turnover in the brainstem, hypothalamus, midbrain and hippocampus. Dopamine turnover was decreased in the brainstem and striatum of NPY-treated rats. Although alpha-MPT did not seem to affect the turnover of serotonin, the concentration of this amine after the administration of NPY was higher in the brainstem, hypothalamus and striatum. Our results suggest that NPY may play a role in the modulation of monoamine turnover in the central nervous system.

Animals↗

PubMed1987

Angiography with fluorescein-labeled dextrans in a primate model of uveitis.

Sequential fluorescein angiography, using fluorescein-labeled dextran molecules of several different sizes, was carried out in monkeys with intraocular inflammation induced with interphotoreceptor retinoid-binding protein. The vascular leakage seen with the dextrans was compared with that seen with standard fluorescein sodium angiography. The angiograms demonstrated that different-sized leaks appear in the retinal vessels in adjacent areas during the course of the inflammation. Most retinal vessels leaked only fluorescein sodium and no dextran of any size, suggesting that it is the unbound fluorescein that leaks out of these vessels and not fluorescein bound to plasma albumin. It was not possible to tell by clinical examination which areas would leak the larger-molecular weight tracers. Ultrastructural studies of the veins leaking the dextrans revealed areas of abnormal endothelial tight junctions, whereas the tight junctions were normal in areas where leakage occurred with fluorescein alone.

Animals↗