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Biomedical subjects

I M Jackson

Publications and source records attributed to I M Jackson.

At least 127 records · Page 7Linked to original sources

Regulation of thyrotropin-releasing hormone secretion from frog skin.

The regulation of TRH secretion from skin fragments of the leopard frog, Rana pipiens, was examined under various conditions. TRH secretion is under dual neurotransmitter control with stimulatory noradrenergic and inhibitory dopaminergic components; other neurotransmitters were generally without effect. Membrane-depolarizing conditions required the presence of calcium to cause TRH release consistent with a stimulus-secretion coupling mechanism. However, the norepinephrine-stimulated response appeared to be independent of external Ca++. TRH secretion was unresponsive to somatostatin, T3, and dibutyryl cAMP, substances which may affect TRH secretion in the mammalian hypothalamus. Anuran skin is a complex secretory tissue, but the presence of large quantities of TRH and other biologically active neuropeptides makes this tissue an attractive model to study the regulation of neuropeptide secretion.

Acetylcholine↗

Immunohistochemical localization of thyrotropin-releasing hormone in the rat hypothalamus and pituitary.

The distribution of immunoreactive TRH in the rat hypothalamus and pituitary was demonstrated using the peroxidase-antiperoxidase technique after rapid fixation of the rat brain with 5% acrolein. Widespread reaction product was identified in neuronal processes throughout the hypothalamus, with dense labeling in the median eminence, dorsomedial nucleus, parvocellular division of the paraventricular nucleus, perifornical region, periventricular nucleus, and organum vasculosum of the lamina terminalis. A striking accumulation of immunoreactive TRH was also noted throughout the posterior pituitary, where fibers appeared to terminate in grape-like swellings. Peroxidase-positive perikarya were best seen after colchicine pretreatment and were distributed in many regions of the hypothalamus. The greatest density of immunoreactive neurons was in the suprachiasmatic preoptic nucleus, parvocellular subdivision of the paraventricular nucleus, perifornical region, dorsomedial nucleus, and baso-lateral hypothalamus. These data are consistent with the role of TRH as a hypophysiotropic hormone, a regulator of the posterior pituitary, and a neurotransmitter or neuromodulator of neurons in other regions of the hypothalamus.

Animals↗

Calcium dependency of potassium-stimulated thyrotropin-releasing hormone secretion from rat neurohypophysis in vitro.

The role of Ca2+ on the K+ -stimulated release of thyrotropin-releasing hormone (TRH) from rat neurohypophysis, stalk median eminence (SME) and hypothalamic fragments in vitro was studied. High K+ (50 mM) caused a significant increase (2-6-fold) in TRH release from all three tissues, (P less than 0.05-0.01), and this effect was inhibited (by 62-80%) on removing Ca2+ (1.8 mM) from the medium (P less than 0.01). The calcium dependency of the TRH response to a membrane depolarizing stimulus (high K+) is consistent with TRH release occurring by a neurosecretory process from the neurophypophysis, as well as from hypothalamic tissue.

Animals↗

Thyrotropin-releasing hormone in the systemic circulation of the neonatal rat is derived from the pancreas and other extraneural tissues.

Thyrotropin-releasing hormone immunoreactivity (IR-TRH) has been detected in the circulation of the neonatal rat. This immunoreactivity was demonstrated in purified ethanol extracts of plasma, and was indistinguishable from synthetic TRH using radioimmunoassay and chromatographic criteria. To determine the source of the circulating IR-TRH, tissue concentrations of TRH were analyzed during maturation of the rat. These studies revealed that during the first 10 d of life, the pancreas contained the greatest concentration of IR-TRH of any organ (pancreas, 289+/-35 pg/mg; hypothalamus, 13+/-3 pg/mg, day 5). Thereafter, pancreatic IR-TRH concentrations declined progressively while hypothalamic concentrations gradually increased (pancreas, 1.2+/-0.2 pg/mg; hypothalamus, 365+/-54 pg/mg, adult rat). IR-TRH was also found throughout the gastrointestinal tract but was not detected in the liver, spleen, kidney, or heart. IR-TRH from the pancreas and gastrointestinal tract gave radio-immunoassay binding displacement curves that were parallel to a curve generated with synthetic TRH, and co-migrated with synthetic TRH on Sephadex G-10 and high performance liquid chromatography. In addition, IR-TRH from purified pancreatic extracts was biologically active in that it released thyrotropin and prolactin from rat adenohypophysial cells maintained in monolayer culture. When a total pancreatectomy was performed on the 5th d of life of the rat, mean plasma TRH concentrations were significantly decreased 3 h afterwards (84+/-9 vs. 63+/-7 pg/ml, P < 0.05). Neither the TRH concentrations in the brain, hypothalamus, or gastrointestinal tract, nor the pituitary-thyroid axis were affected by the pancreatectomy. However, mean plasma TRH concentrations remained unaltered 3 h after removal of the hypothalamus and extrahypothalamic brain. FROM THESE RESULTS WE CONCLUDE THE FOLLOWING: (a) the TRH immunoreactivity in the circulation, pancreas, and gastrointestinal tract of the neonatal rat is indistinguishable from synthetic TRH; (b) pancreatic secretion provides a significant contribution to the IR-TRH in plasma, and a proportion of the circulating IR-TRH is derived from other extraneural sites. These findings therefore imply that alterations in hypothalamic and extrahypothalamic brain secretion of TRH are not reflected by changes in levels of this tripeptide in the systemic circulation.

Age Factors↗

Abundance of immunoreactive thyrotropin-releasing hormone-like material in the alfalfa plant.

Immunoreactive TRH (IR-TRH) is found in high concentrations (157 +/- 6 ng/g) in extracts of a plant, alfalfa. On high performance liquid chromatography (HPLC), most alfalfa TRH showed an increased retention time compared to synthetic TRH. Since the plant extract eluted after synthetic TRH on both Sephadex G-10 and Biogel P-2 chromatography, it does not appear to be an aggregate or a "big" TRH. Incubation with rat serum caused degradation of alfalfa TRH at a rate similar to synthetic TRH. Since the antibody against TRH is highly specific for the N and C terminal ends of the molecule, a point change at the His could explain the nature of alfalfa TRH. The biologic function of material resembling a mammalian hypothalamic releasing factor in this location is unknown, but its presence in the plant kingdom may have evolutionary significance.

Animals↗

Growth hormone secretory status is a determinant of the thyrotropin response to thyrotropin-releasing hormone in euthyroid patients with hypothalamic-pituitary disease.

To assess the influence of endogenous GH secretion on the TSH and T3 responses to TRH administration in patients with hypothalamic-pituitary disease, we analyzed tests in a selected group of 26 euthyroid patients with hypothalamic-pituitary disease and in 15 normal controls. Basal TSH levels and the TSH response to TRH were significantly greater in GH-deficient patients (group 1) than in patients with normal anterior pituitary function and unimpaired GH reserve (group II). However, the T3 response to TRH was significantly less in group 1 than in group II patients. In acromegaly (group III), the TSH response to TRH was blunted, while basal and stimulated T3 levels were no different compared to control levels. These findings suggest that endogenous GH depresses the TSH response to TRH while enhancing the thyroid secretion of T3 in response to the evoked TSH released.

Adolescent↗

Bromocriptine therapy in acromegaly: use in patients resistant to conventional therapy and effect on serum levels of somatomedin C.

Seven patients with clinically active acromegaly who had not responded completely to previous surgical or radiation therapy were treated with bromocriptine. Bromocriptine was well tolerated; only one of the seven patients discontinued treatment secondary to side effects. Six of the seven patients improved during bromocriptine therapy, although GH levels were normalized in only two patients. All patients had elevated levels of somatomedin C (Sm-C) before therapy even when basal levels of GH were less than 10 ng/ml. One patient normalized both GH and Sm-C during bromocriptine therapy and had an excellent clinical response. Five patients had moderately good clinical responses; four of these patients had substantial falls in GH levels, but Sm-C levels fell minimally if at all in four and actually increased in one patient. In one patient, there was no change in clinical status, GH levels, or Sm-C levels. Thus, the clinical response did not correlate well with changes in Sm-C in most patients. The patterns of response to provocative stimuli of GH secretion in acromegaly were maintained during bromocriptine therapy, as has been previously been reported. Based on our experience, bromocriptine appears to be a useful adjunct in the therapy of acromegaly, even in patients who have had prior ablative therapy.

Acromegaly↗

Evolutionary significance of the phylogenetic distribution of the mammalian hypothalamic releasing hormones.

The hypophysiotrophic hormones isolated from the mammalian hypothalamus are distributed throughout the nervous system of vertebrate species. Although their role in regulating pituitary hormone secretion in mammals is clear, a similar function in lower species has not been established. Thyrotropin-releasing hormone is unable to stimulate thyroid function in amphibia and fish, despite being present in the hypothalamus and brain of these species of high concentration. The tripeptide is also found in high concentration in frog skin, a tissue derived from (or programed by) primitive neuroectoderm that is also a rich source of other peptides structurally related to neural peptides located in mammalian brain and gut. Luteinizing hormone-releasing hormone (LHRH) is able to activate gonadotropin secretion in submammalian species but there is evidence that the LHRH material present in avian, reptilian, and piscine brain is not identical to the mammalian decapeptide. An LHRH-like material present in frog sympathetic ganglia appears to function as a neurotransmitter in this location. Somatostatin is present in high concentrations in the hypothalamus, brain, pancreas, and gastrointestinal tract of all vertebrates and chromatographically is identical to the mammalian material, suggesting that this peptide is an "ancient" molecule with an important role in neuronal pancreatic and digestive function. The hypothalamic releasing hormones are part of a family of neural peptides that have a widespread anatomic and phylogenetic distribution and form a diffuse neuroendocrine system. It an material, suggesting that this peptide is an "ancient" molecule with an important role in neuronal pancreatic and digestive function. The hypothalamic releasing hormones are part of a family of neural peptides that have a widespread anatomic and phylogenetic distribution and form a diffuse neuroendocrine system. It an material, suggesting that this peptide is an "ancient" molecule with an important role in neuronal pancreatic and digestive function. The hypothalamic releasing hormones are part of a family of neural peptides that have a widespread anatomic and phylogenetic distribution and form a diffuse neuroendocrine system. It appears likely that the releasing hormones initially arose with a neurocrine or paracrine function, and that only later in evolution did they acquire the role of regulating adenohypophysial secretion.

Amphibians↗

Galactorrhea, oligo/amenorrhea, and hyperprolactinemia in patients with craniopharyngiomas.

We report three patients with craniopharyngiomas who had galactorrhea, oligo/amenorrhea, and abnormal sellar tomograms, clinically suggesting the presence of a prolactinoma. One patient had an intrasellar craniopharyngioma (Rathke's cleft cyst) diagosed during surgical exploration of the pituitary fossa for removal of a suspected prolactinoma, and two had suprasellar caraniopharyngiomas whose presence was suspected on the basis of computed tomography. This finding emphasizes the importance of computed tomography in the evaluation of patients with the clinical presentation of a prolactinoma. In two patients, PRL levels were elevated before surgery and remained elevated after removal of the craniopharyngioma. In the third case, an initially normal serum PRL level became elevated after removal of the tumor.

Adult↗

Response of adult male rats to LH-RH after neonatal immunization with antiserum to LH-RH.

Male rats were passively immunized at Day 5 of age with LH-RH antiserum. Their response to LH-RH at 100 days of age was examined. Serum FSH and LH concentrations increased more than in control rats, although basal plasma levels were similar. The pituitary content of LH, but not FSH, was significantly increased, and hypothalamic content of LH-RH was similar in both groups. The testes and seminal vesicles were smaller in experimental animals than in controls. It is suggested that transient blockade of LH-RH secretion during the neonatal period produces abnormalities in pituitary-testicular functon in the adult rat.

Animals↗