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Biomedical subjects

J F Wilber

Publications and source records attributed to J F Wilber.

At least 73 records · Page 4Linked to original sources
PubMed1983

Developmental changes in the distribution of rat brain pyroglutamate aminopeptidase, a possible determinant of endogenous cyclo(His-Pro) concentrations.

The distribution of cyclo(His-Pro), thyrotropin-releasing hormone (TRH) and Pyroglutamate aminopeptidase activity in adult and developing rat brains were studied. A comparison of the subcellular distribution of Pyroglutamate aminopeptidase activity in hypothalamic and cerebral cortical extracts from adult rats exhibited remarkable differences. In hypothalamus, the enzyme activity was mainly associated with the soluble fraction whereas in cortex it was predominantly associated with the particulate fractions. During postnatal development, the brain concentrations of cyclo(His-Pro) and Pyroglutamate aminopeptidase activities declined with age. These data suggest that Pyroglutamate aminopeptidase activity, but not TRH, plays an active role in determining the levels of endogenous cyclo(His-Pro) concentrations in brain.

Aging↗
PubMed1983

Influence of the pineal gland on hypothalamic content of TRH in the Syrian hamster.

Blinding adult female hamsters by bilateral orbital enucleation caused an increase in thyrotropin-releasing hormone (TRH) content of the medial basal hypothalamus and also led to an increase in TRH content in the remainder of the hypothalamus (dorsal hypothalamus). Although pinealectomy by itself had no significant effect on the neuroendocrine-thyroid axis, this surgical procedure prevented the inhibition of serum thyroxin observed in blinded hamsters. Pinealectomy also prevented the increase in TRH content of medial basal and dorsal hypothalamus observed in blinded hamsters. The results are consistent with the view that the pineal gland has a CNS site of action and provide evidence that the anti-thyroid influence of the pineal gland can be explained by pineal inhibition of TRH release.

Animals↗
PubMed1983

Dynamics of serum thyrotropin and thyroid hormone changes in fasting.

This study was designed to address the question of whether decreased hypothalamic TRH secretion was responsible for the transient decline in serum TSH levels characteristic of the early phase of fasting in man. Changes in serum TSH, total T4 (TT4), free T4 (FT4), and total T3 (TT3)/TT4 and total rT3(TrT3)/TT4 ratio values together with plasma TRH levels were evaluated before, during, and after a constant 48-h infusion of either TRH (75 ng/min), or saline, initiated at 10 h into a 6-day fast, in groups of six ambulating, mildly obese female subjects. On the first day of the fast, no change in serum TSH levels was seen with saline infusion relative to control, whereas mean TSH levels rose 2 1/2-fold with TRH infusion. On the second day of the fast, serum TSH levels simultaneously declined in both the saline- (43%, P less than 0.005) and TRH- (52%, P less than 0.005)-infused groups relative to the previous day. On the third day of the fast, after stopping the infusions, mean serum TSH levels fell below control in both the saline- and TRH-treated groups, but subsequently returned to prefasting levels. A distinct circadian pattern of TSH release was present throughout the study. Plasma TRH values were unaffected by fasting in the saline-infused group, but rose 2 1/2-fold in the TRH-infused group. The sequence of changes in the serum thyroid hormone indices were similar for the two groups: a rapid rise in FT4 was followed by a gradual fall in TT3/TT4 ratios during the first 24 h of fast, which was followed by a rise in TrT3/TT4 ratios after 48 h of fast. This study in fasting, mildly obese females suggests that: 1) The transient suppression of serum TSH during early fasting is not TRH mediated. 2) Fasting does not alter plasma TRH levels. 3) A temporal sequence of changes in serum thyroid hormone indices occurs in fasting, this being an initial rise in FT4 (10 h) followed by a fall in both serum TT3/TT4 (12-14 h) and TSH (30-36 h) and finally by a rise in TrT3/TT4 levels (48 h). This sequence of events suggests that the initial inhibition of serum TSH levels in early fasting results from the acute elevation in FT4 levels, and that the reestablishment of normal serum TSH levels with continued fasting is associated with declining serum TT3 levels.

Adult↗
PubMed1982

Cyclo (His-Pro): mapping hypothalamic sites for its hypothermic action.

Hypothalamic loci of Sprague-Dawley rats were individually injected with cyclo (His-Pro) to determine the sites where that metabolite of thyrotropin-releasing hormone acts to produce hypothermia. There was almost always a positive hypothermic response in the preoptic-anterior hypothalamic area (POA/AHA); injection into the posterior or middle hypothalamic areas or into the hippocampus caused no significant decrease in core temperature. The fact that only injection into the POA/AHA evoked hypothermia suggests that this area is a major hypothalamic site of action of cyclo (His-Pro) in modulating thermoregulation in the rat.

Animals↗
PubMed1982

Regional dissociation of histidyl--proline diketopiperazine (cyclo-(His--Pro)) and thyrotropin-releasing hormone (TRH) in the rat brain.

The concentration of cyclo-(His--Pro) and its precursor, thyrotropin-releasing hormone (TRH) were measured in seven different areas of rat brain using specific radioimmunoassays. Although the concentration of both of these peptides was highest in the hypothalamus, their distribution patterns in all other loci of the brain were dissimilar. These results suggest that factors in addition to TRH concentrations are important in determining the unique concentration pattern of cyclo-(His--Pro) in the brain.

Animals↗
PubMed1982

Chronic alcohol consumption increases cyclo (His-Pro)-like immunoreactivity in the rat brain.

Administration of histidyl-proline diketopiperazine (cyclo (His-Pro)) to rats attenuates ethanol-induced sleep. To understand the role played by cyclo (His-Pro) in the pathophysiology of prolonged alcohol consumption, we have measured the distribution of this peptide in brains of control and alcohol-treated rats. The data show that prolonged alcohol consumption increases the concentration of cyclo (His-Pro) in hypothalamic as well as extrahypothalamic brain. These changes may reflect a physiologic adaptation of the brain during alcohol consumption.

Alcoholism↗
PubMed1982

Thyrotropin-releasing hormone: its distribution and metabolism during development in bullfrog (Rana catesbeiana).

The development changes in the metabolism of thyrotropin-releasing hormone (TRH), cyclo (His-Pro) formation from TRH, and the levels of endogenous TRH in frog brain and skin were determined. The results indicated that TRH concentrations were considerably higher in brain than in skin, and in both of these structures TRH content increased significantly following metamorphosis to adulthood. This increase in TRH concentration is probably a reflection of a marked decrease in TRH-metabolism in adult frogs compared to tadpoles. However, the formation of cyclo (His-Pro) from TRH increased during the developmental period reaching to a maximum in adulthood. The possible role of cyclo (His-Pro) in the amphibian developmental process is discussed in relation to our recent observation showing cyclo (His-Pro) inhibition of prolactin secretion.

Animals↗
PubMed1982

Measurements of thyrotropin-releasing hormone-like material in human peripheral blood by affinity chromatography and radioimmunoassay.

TRH measurements have been carried out in human peripheral blood and rat peripheral and portal blood by RIA in conjunction with affinity chromatography. Human peripheral blood TRH appeared to be identical to synthetic TRH by immunological, chromatographic, and enzymatic criteria. TRH concentrations in normal subjects ranged from 24-138 pg/ml, with a mean of 78 pg/ml. Moreover, TRH concentrations were not altered from normal in either thyrotoxic or hypothyroid subjects. TRH measurements in selected venous compartments in the rat, in conjunction with previously reported kinetic data, suggest that most of the TRH in peripheral blood is derived from nonhypothalamic sources.

Animals↗
PubMed1981

Effects of thyroidectomy, propylthiouracil, and thyroxine on pituitary content and immunocytochemical staining of thyrotropin (TSH) and thyrotropin releasing hormone (TRH).

Previous studies have demonstrated immunocytochemical staining for beta chains of thyroid stimulating hormone (TSH-beta) in rough endoplasmic reticulum of pituitary cells hypertrophied after thyroidectomy ("thyroidectomy cells") (Moriarty CG(1976): J Histochem Cytochem (24:846; Moriarty GC, Tobin RB (1976): J Histochem Cytochem 24:1140). Here we report the localization of thyrotropin releasing hormone (TRH) in serial sections of the same pituitaries to determine if it could be found at similar sites. No staining for TRH was found in hypertrophied TSH cells formed 42 days after the surgery, or after 14, 34, and 70 days of propylthiouracil (PTU) treatment. The loss in immunostaining in the PTU-treated rats was correlated with radioimmunoassay (RIA) measurements that showed a 65% reduction in anterior pituitary TRH content after 34, 70, and 98 days of PTU treatment (from 22.9--7.8 pg/mg wet wt) and a 50% reduction in TSH content after 34 days of treatment. When thyroxine was administered to hypothyroid rats for 3 days before death, our previous studies had demonstrated intense staining for TSH in granules inside the rough endoplasmic reticulum. In this study, the radioimmunoassay showed that TSH content rose dramatically in the hypothyroid animals treated with PTU for 77 days and thyroxine for 2 days before death (from 8.5--64.1 mU/mg wet wt); however, the rise in TRH content was minimal (5.8--9.8 pg/mg wet wt). The immunocytochemical stain for TRH correlated well with the RIA showing a weak reaction mainly on small granules in the cytoplasm. No reaction for TRH was found in rough endoplasmic reticulum. These results suggest that TRH and TSH storage sites are dissimilar in the hypothyroid rat. The presence of stain for TRH in granules in the cytoplasm suggests that it might play a role in the storage or packaging of TSH. Its absence in profiles of rough endoplasmic reticulum staining intensely for TSH suggests that it is not synthesized at this site. No definite conclusions about its origin can be drawn at this time.

Animals↗
PubMed1980

Regional distribution of leucine-enkephalin in hypothalamic and extrahypothalamic loci of the human nervous system.

The recent discovery of the endogenous opioid peptide, leucine-enkephalin (L-E), throughout vertebrate species prompted investigation of its potential presence in the human CNS using a specific radioimmunoassay. Twenty CNS structures were dissected from 5 human brains obtained at autopsy and were extracted with 2 N and glacial acetic acid. L-E immunoreactivity, identical to synthetic standard, was found in all structures examined. Highest concentrations (range 76-650 pmol/g wet wt.) were found in the pituitary, infundibular stalk, globus pallidus, putamen, substantia nigra, amygdala, head of caudate, and hypothalamus. Lowest concentrations (range 23-49) were found in frontal cortex and cerebellum. L-E was also found in the spinal cord. It is concluded that L-E immunoreactivity is present in the human CNS. The correspondence between the distribution of L-E and the opiate receptor suggests that L-E represents a biologically significant endogenous opiate in man. The high concentrations of L-E in the human hypothalamus and pituitary raises the possibility of a neuroendocrine role for this peptide.

Brain Chemistry↗
PubMed1979

The identification of gonadotropin-releasing hormone (GnRH) in hypothalamic and extrahypothalamic loci of the human nervous system.

Immunoreactive-like GnRH activity has been identified in 24 of 26 separate loci of the human central nervous system. Tissues, secured from 5 brains at autopsy, were dissected, extracted sequentially with 2N and glacial acetic acid, lyophilized, and eluted in buffered saline for GnRH determinations by specific radioimmunoassay. GnRH concentrations (ng/mg protein) ranged from 8.96 (infundibulum) to 0.001 (cerebellum. middle lobe). Highest extrahypothalamic concentrations of GnRH were found in mamillary body (0.076) and thalamus (0.002). Extrahypothalamic GnRH was identical to synthetic and hypothalamic GnRH by criteria of immunoidentity. No post-mortem GnRH peptidolysis, evaluated experimentally in rats, was evident between 0 and 16 hrs in intact tissues maintained at 4 degrees C. These data suggest that GnRH is distributed throughout regions of the human brain outside the hypothalamus and suggest new, non-endocrine functions for GnRH in the human CNS, analogous the those reported recently for GnRH in experimental animals.

Aged↗