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Biomedical subjects

I M Jackson

Publications and source records attributed to I M Jackson.

At least 109 records · Page 6Linked to original sources
PubMed1985

Thyrotropin releasing hormone but not histidyl-proline diketopiperazine is depleted from rat spinal cord following 5,7-dihydroxytryptamine treatment.

Histidyl-proline diketopiperazine (His-Pro DKP) has been proposed as a metabolite of thyrotropin releasing hormone (TRH). Since spinal cord TRH arises from serotoninergic (5-HT) neurons in the brainstem, a 5-HT neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT), was injected into the lateral ventricle of 7 rats, and the levels of TRH and His-Pro DKP in the spinal cord were studied 5 weeks later. In comparison to the saline treated controls, 5,7-DHT treated animals showed marked depletion of TRH throughout the spinal cord, especially in the lumbosacral area where almost 90% disappeared, (0.28 +/- 0.02 vs. 2.46 +/- 0.01 ng/mg protein; P less than 0.0001). In contrast, His-Pro DKP showed no significant change in any region. Since 5,7-DHT lowers spinal cord TRH by destroying TRH perikarya in the medulla, we conclude that spinal cord His-Pro DKP is not derived from the same neurons as TRH.

5,7-Dihydroxytryptamine↗
PubMed1985

Immunoreactive neuronal pathways of growth hormone-releasing hormone (GRH) in the brain and pituitary of the teleost Gadus morhua.

Using an antiserum directed against the C-terminus of hGRH(1-44)NH2 and another recognizing the mid portion to C-terminal of hGRH(1-40)OH, we identify two immunocytochemically distinct GRH-immunoreactive systems in the brain of the codfish, Gadus morhua. The antiserum directed against GRF(1-44)NH2 stains cell bodies exclusively in the rostral pars distalis. The other antiserum immunoreactive with GRF(1-40)OH reacts with a population of parvocellular and magnocellular neuronal cell bodies in the hypothalamus and with two major axonal pathways which project toward the median eminence and terminate primarily in the pars nervosa. These results indicate the presence of at least two forms of hGRH-like peptides in the teleost which may have different roles in the regulation of pituitary function.

Animals↗
PubMed1985

Multiple forms of human pancreatic growth hormone releasing factor-like immunoreactivity in teleost brain and pituitary.

Two anatomically distinct neuronal GRF systems in the brain-pituitary of the teleost codfish (Gadus morhua), immunohistochemically localized by use of antisera directed against hpGRF1-44NH2 and hpGRF1-40OH are described. Chromatographic analysis additionally revealed the presence of three molecular variants of immunoreactive hpGRF1-44NH2, two of which differ from the authentic human material. However, all three forms released GH from rat pituitary cells in dispersed culture. These findings indicate that hpGRF is highly conserved in nature and suggest that peptides closely related to this human hypothalamic releasing hormone regulate the teleost pituitary.

Animals↗
PubMed1985

Thyrotropin-releasing hormone release from rat pancreas is stimulated by serotonin but inhibited by carbachol.

Immunoreactive TRH (IR-TRH) has been found in the mammalian pancreas, with several studies documenting high concentrations in the late fetal/early neonatal period. As the factors regulating pancreatic TRH synthesis and release have not been fully explored, we developed a monolayer culture system of dissociated fetal/neonatal rat pancreatic cells to study the release of TRH from the mammalian pancreas. IR-TRH was detected in the culture medium and the IR material appeared authentic based on parallelism with synthetic TRH in RIA and retention time on HPLC. Potassium-induced depolarization (60 mM KCl) resulted in a 170% increase in TRH release compared to that by the Krebs-Ringer bicarbonate control (P less than 0.05). Serotonin stimulated TRH release, with the maximal effect seen with 10(-6) M (130% increase compared to control; P less than 0.05). Carbachol resulted in a dose-dependent inhibition of TRH release (57% inhibition of release at 10(-8) M; P less than 0.01 compared to control). There was no effect on release with norepinephrine, epinephrine, dopamine, gamma-aminobutyric acid, or histamine. We conclude the following. 1) Authentic TRH is secreted by fetal/neonatal rat pancreatic cells in culture. 2) The secretion of TRH is stimulated by potassium-induced depolarization in a calcium-dependent manner, suggesting a classic neurosecretory process of release. 3) The secretion of pancreatic TRH may be under specific neurotransmitter control, with serotonin stimulating and acetylcholine inhibiting release of the tripeptide.

Animals↗
PubMed1984

Distribution of immunoreactive growth hormone releasing factor(1-44)NH2 in the tuberoinfundibular system of the rhesus monkey.

Using an antiserum which reacts with the carboxyl terminus of GRF(1-44)NH2, the distribution of immunoreactive growth hormone releasing factor (GRF) in the rhesus monkey hypothalamus was delineated by peroxidase immunocytochemistry. Immunoreactive material was present in dense terminal fields in the median eminence closely associated with portal capillaries but in a location distinct from that noted for immunoreactive thyrotropin-releasing hormone (TRH) or somatostatin. GRF-immunoreactive cell bodies were identified in the arcuate nucleus and ventromedial nucleus. These studies provide evidence for the presence of GRF(1-44)NH2 in the primate brain and demonstrate that in the hypothalamus it is localized exclusively in cells and fibers corresponding to the tuberoinfundibular system.

Animals↗
PubMed1984

The distribution of thyrotropin-releasing hormone (TRH) in the rhesus monkey spinal cord.

The distribution of thyrotropin-releasing hormone (TRH) in the Rhesus monkey spinal cord was studied using a highly specific antibody to TRH and the indirect peroxidase-antiperoxidase technique. TRH-positive fibers were found at all levels of the spinal cord and were in greatest concentration in the ventral gray, intermediolateral column and central gray. All motor nuclear groups in lamina IX of the ventral gray were innervated by TRH, frequently in close association with perikarya of alpha-motoneurons. The motor nuclei in the lumbar cord were the most heavily stained and contrasted to the minimal staining in the retrodorsolateral nuclear groups of the cervical, thoracic and sacral cord. Within the intermediolateral column, which contains the majority of preganglionic sympathetic neurons, TRH terminal fields reached their highest density between T2-T4 and T12-L2. Other preganglionic neurons including the nucleus intercalatus spinalis and the dorsal commissural nucleus were also densely innervated. These studies demonstrate the preferential distribution of TRH in the monkey spinal cord to regions containing alpha-motoneurons and preganglionic neurons and indicate that TRH may play an important role in the regulation of motor function and in the autonomic nervous system.

Animals↗
PubMed1984

Rat anterior pituitary cells maintained on artificial capillaries: responses of thyrotrophs and lactotrophs to depolarization, TRH and dopamine.

Rat anterior pituitary cells have been maintained over an 18-day period in a perfusion system designed around artificial capillaries. Using novel methodology the cells have been visualized by light microscopy and appear as aggregates, closely attached to and sometimes stretching around the capillaries. Their morphology is consistent with previous histology at the level of light microscopy. The techniques described are compatible with immunohistochemistry and electron microscopy. The functional integrity of thyrotrophs and lactotrophs maintained in the system has been examined by measuring the dynamics of TSH and PRL secretion in response to depolarization, TRH and dopamine (DA). TSH and PRL were significantly and reproducibly released by TRH over a 7-day period. On each day the release was dose-dependent with a threshold of at least 28 pg. Qualitatively the responses were rapid in onset (within minutes) for both hormones. Similar responses were measured in response to high K+ depolarization. Basal secretion of TSH and PRL was rapidly and significantly inhibited by DA in a dose-dependent manner (ED50 20 +/- 25 nM for TSH and 70 +/- 40 nM for PRL). Inhibition was dependent on the continued presence of DA and could be mimicked by bromocriptine and stereospecifically prevented by the active but not the inactive isomer of the DA receptor antagonist butaclamol. Simultaneous administration of 10(-6) M DA with 10(-8) M TRH prevented the release of TSH and PRL. The effect of DA was transient, subsequent TRH responses being qualitatively and quantitatively normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Efficacy and tolerability of oral acetylcysteine (Fabrol) in chronic bronchitis: a double-blind placebo controlled study.

This multicentre, double-blind, placebo controlled, between-patient study in general practice in the United Kingdom examined the effect of oral N-acetylcysteine (Fabrol) on the symptomatology of patients with chronic bronchitis over a 3-month period. Although improvement in subjective symptoms (sputum viscosity and character, difficulty in expectoration and cough severity) occurred in both treatment groups over the trial period, improvements in difficulty in expectoration and cough severity were greater in patients receiving N-acetylcysteine compared to matching placebo. Trial medication was well tolerated, with a greater number of side-effects attributed to therapy occurring in patients receiving placebo.

Acetylcysteine↗
PubMed1984

Ontogeny of thyrotropin-releasing hormone and histidyl proline diketopiperazine in the rat central nervous system and pancreas.

The ontogeny of TRH and of a proposed TRH metabolite, histidyl proline diketopiperazine (His-Pro DKP), was determined in the rat central nervous system and pancreas as a means of studying the interrelationship of these peptides. Various regions of the rat brain, spinal cord, and pancreas were dissected from animals ranging in age from prenatal day 17 to adult. The tissues were extracted for TRH and His-Pro DKP, and tissue levels of the two peptides were measured by specific RIAs. We found increasing TRH levels in the hypothalamus, spinal cord, and multiple extrahypothalamic brain regions in the developing rat [e.g. from 21 +/- 3 (+/- SE) pg/hypothalamus on prenatal day 17 to 2606 +/- 296 pg/hypothalamus in the adult]. In the rat pancreas, however, TRH levels initially increased from 354 +/- 37 pg/pancreas on prenatal day 21 to 749 +/- 68 pg/pancreas on postnatal day 7, but from day 7 to adulthood, the TRH content fell dramatically, being undetectable in the adult rat pancreas. The His-Pro DKP content increased in nearly all tissues studied, with peak values occurring on postnatal days 10 and 28 and in the adult. There was little apparent correlation, however, between the anatomical distribution and ontogeny of TRH compared with those of His-Pro DKP. We conclude that His-Pro DKP and TRH have widespread distributions involving the hypothalamus, extrahypothalamic brain, spinal cord, and pancreas in the developing rat. TRH and His-Pro DKP, however, have differing patterns of ontogeny in the rat, suggesting that His-Pro DKP may be derived from sources other than just TRH.

Animals↗
PubMed1984

Use of a rapid, sensitive immunoradiometric assay for thyrotropin to distinguish normal from hyperthyroid subjects.

Using a new three-site immunoradiometric assay for thyrotropin (TSH), we measured concentration of this hormone in the serum of 47 patients with hyperthyroidism and 46 controls. The mean and range of serum TSH concentration was significantly lower in thyrotoxic than in control subjects, and it was possible to correctly identify 96% of thyrotoxic patients on the basis of a serum TSH concentration less than 0.5 milli-int. unit/L. We conclude that such measurement is highly sensitive for distinguishing hyperthyroid from normal subjects, and that the lower limit of normal for TSH in serum is about 0.5 milli-int. unit/L.

Humans↗
PubMed1983

Evidence that spinal cord thyrotropin-releasing hormone is independent of the paraventricular nucleus.

To determine whether neuronal perikarya containing thyrotropin-releasing hormone (TRH) in the paraventricular nucleus project to the spinal cord, this region of the hypothalamus was ablated by a midline electrolytic lesion and the spinal cord assayed for its content of TRH. In contrast to the marked diminution of TRH in the median eminence, there was no significant change in the TRH content in the spinal cord. These results indicate the absence of significant afferent input of TRH-containing perikarya in the paraventricular nucleus to the spinal cord.

Animals↗
PubMed1983

Investigation of hypothalamic-pituitary disease.

It can be readily appreciated from the preceding discussion that many endocrine and non-endocrine tests are available for the evaluation of patients with suspected hypothalamic-pituitary disease. The endocrine evaluation of these subjects should be tailored according to the type and extent of pathology suspected (see Tables 2 and 3). For patients with pituitary adenomas and clinical features of hyperpituitarism, such as hyperprolactinaemia, Cushing's disease or acromegaly, the initial tests should be directed at the hormone whose excess is suspected. For example, a glucose suppression test for acromegaly or dexamethasone suppression test for Cushing's disease should be performed early in the evaluation. The possibility of deficiencies of the other pituitary hormones should then be addressed in patients with secretory tumours, but initially in those with apparent non-functioning adenomas. In patients with large macroadenomas pituitary hormone deficiencies are almost invariable with GH and FSH/LH being the most commonly affected, followed by TSH and ACTH in that order (Snyder et al, 1979a; Valenta et al, 1982). Basal thyroid function tests, serum oestradiol or testosterone, and basal gonodotrophins should be routinely obtained in patients with macroadenomas. Additionally, the integrity of the pituitary-adrenal axis should be determined and an overnight water deprivation test for assessment of neurohypophyseal function is also recommended. GH stimulation testing is valuable as a test of pituitary function in patients with suspected pituitary tumours since GH reserve is lost very early in the development of hypopituitarism. Evaluation of the pituitary-thyroid axis with TRH or the pituitary gonadal axis with LHRH generally provides limited additional information of diagnostic value in individual patients with macroadenomas. However, the 'paradoxical' responses to TRH and LHRH may be useful as a biological marker following therapy in patients with GH- or ACTH-secreting tumours. In patients with microadenomas, pituitary hormone deficiencies are uncommon (Valenta et al, 1982). Despite this observation, it may be beneficial to determine basal thyroid levels, gonadotrophin levels, serum testosterone or oestradiol levels, and the response to an overnight metyrapone test in such patients to provide a baseline for future care.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenocorticotropic Hormone↗
PubMed1983

Characterisation of somatostatin and TRH release by rat hypothalamic and cerebral cortical neurons maintained on a capillary membrane perfusion system.

We have investigated the nature of the immunoreactive somatostatin (SS) and thyrotropin-releasing hormone (TRH) produced by long-term capillary perfusion cultures of rat fetal cortical and hypothalamic cells. Dispersed cortical and hypothalamic cells from 17-day-old fetal rats were injected on to the outer surfaces of separate capillary membrane perfusion systems. Recirculating nutrient medium (Minimum Essential Medium with added glucose, antibiotics and 10% fetal calf serum) was then perfused via the capillary lumen at a rate of 1.5 ml/min and was changed three times weekly. Medium reservoirs, gaseous exchange coils and capillary columns were maintained in a 95% air/5% CO2 environment with 100% humidity. After 6 and 12 days in continuous perfusion, both cortical and hypothalamic cells demonstrated immuno-reactive SS release following 60 mMK+ depolarization (5- to 7-fold increase from basal secretion levels of 15-20 pg/3 X 10(7) cells/10 min). This response was clearly calcium dependent since it was abolished during washes with Ca2+-free Krebs-Ringer bicarbonate solution. Affinity purified material from pooled neuronal perfusates showed three distinct peaks of somatotropin release-inhibiting factor (SRIF) immunoreactivity following polyacrylamide gel chromatography on Biogel-P10. The dominant form coeluted with synthetic tetradecapeptide-somatostatin (SS-14) and a smaller amount (c 30%) coeluted with synthetic SS-28. (The SS-14 antibody used showed equimolar cross reactivity with SS-28). A larger form of immunoreactive material was also detected with an apparent molecular weight of about 11,500 daltons. Hypothalamic and cortical perfusates produced similar electrophoretic patterns of immunoreactive SS (ISS).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Distribution of immunoreactive human growth hormone-like material and thyrotropin-releasing hormone in the rat central nervous system: evidence for their coexistence in the same neurons.

The distribution of a substance with human GH (hCG)-like immunoreactivity was studied in the rat brain after rapid fixation with acrolein. Using this method of tissue preparation, the hGH-like material (hGH-LM) was found in several hypothalamic and extrahypothalamic regions of the brain and extended into the spinal cord and posterior pituitary. On serial sections, the distribution of the hGH-LM was observed to be identical to that of TRH throughout the neuraxis. Sequential immunostaining of the hGH-LM and TRH in the same tissue section revealed the coexistence of these two peptides in the same neuronal cell bodies in the hypothalamus and brain stem and in beaded processes in all regions of the central nervous system studied. These findings demonstrate the intimate association between the hGH-LM and TRH in the central nervous system and raise the possibility that the hGH-LM forms part of a precursor hormone from which TRH is derived.

Animals↗
PubMed1982

Thyrotropin-releasing hormone in the pancreas and brain of the rat is regulated by central noradrenergic and dopaminergic pathways.

These studies have been undertaken to evaluate the role of the brain noradrenergic and dopaminergic pathways in the regulation of the secretion of thyrotropin-releasing hormone (TRH) in the central nervous system (CNS) and pancreas of the neonatal rat. When CNS stores of norepinephrine (NE) were selectively reduced by the subcutaneous administration of the dopamine-beta-hydroxylase inhibitor FLA-63, TRH concentrations were significantly reduced throughout the brain. However, when CNS stores of both NE and dopamine (DA) were depleted by the subcutaneous administration of the tyrosine hydroxylase inhibitor alpha-methyl-rho-tyrosine (alpha-MT), TRH concentrations in the brain were not significantly altered.FLA-63 and alpha-MT did not significantly reduce pancreatic catecholamine concentrations, indicating that in the basal state, these agents predominantly deplete central catecholamine stores. Nevertheless, pancreatic TRH concentrations were markedly reduced by FLA-63, and this effect was significantly attenuated by the simultaneous intracerebroventricular (icv) administration of NE. In contrast to the effects of FLA-63, alpha-MT caused a significant increase in pancreatic TRH concentrations, and this effect was significantly lessened by icv DA. To determine whether the sympathetic nervous system might be one route by which these central effects are mediated, a chemical sympathectomy was induced with guanethidine. This treatment selectively reduced pancreatic concentrations of NE, and caused a marked increase in pancreatic TRH concentrations. FROM THESE OBSERVATIONS, WE CONCLUDE THE FOLLOWING: (a) within the central nervous system, both NE and DA are involved in regulating brain TRH secretion or biosynthesis, and the direction of action of these two neurotransmitters appears to be opposite; (b) pancreatic TRH secretion or biosynthesis is also controlled by the brain noradrenergic and dopaminergic systems, and the net effects of each of these pathways appears to be opposite; (c) at least one route by which impulses from the brain may travel and modulate pancreatic TRH secretion or biosynthesis is by the sympathetic nervous system.

Animals↗