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Biomedical subjects

L Krulich

Publications and source records attributed to L Krulich.

At least 55 records · Page 3Linked to original sources

Catecholaminergic regulation of TSH and growth hormone release in ovariectomized and ovariectomized, steroid-primed rats.

Third ventricular injection of dopamine (DA), Piribedil (ET-495), a DA receptor stimulator, norepinephrine (NE), epinephrine (E) and systemic administration of larger doses of DA and the receptor stimulant, apomorphine (APM), were used to evaluate their role in the regulation of TSH and GH secretion in ovariectomized (OVX) as well as ovariectomized, estrogen-progesterone treated (OEP) rats. Intraventricular or i.p. injection of DA or its agonists, ET-495, and APM, caused a lowering of plasma TSH and an elevation of plasma GH concentration in OVX as well as in OEP rats. In contrast, intraventricular injection of NE or E increased plasma TSH and GH concentration. On the basis of these results it is concluded that the central dopaminergic system is inhibitory to TSH secretion, as reflected in our exeriments by the significant reduction of TSH levels. On the other hand, the noradrenergic and adrenergic system has a stimulatory role on the release of TRH as evidenced by the increase in plasma TSH levels. Activation of dopaminergic, noradrenergic and adrenergic systems appears to promote release by hypothalamic GH releasing hormone as reflected in the enhanced concentration of plasma GH, but the precise physiological role of these biogenic amines in modulating the release of TSH and GH hormone remains to be elucidated.

Animals↗

The effect of pinealectomy on the pattern of prolactin secretion in conscious freely moving male rats.

Plasma prolactin (Prl) titers were determined by radioimmunoassay in conscious, freely moving male rats which had either had sham operations or had been pinealectomized. Values were determined during the day and during the night in animals on a reversed light cycle. During the day plasma Prl levels were low in both groups with small bursts and a tendency for greater elevation toward the end of the collection period at 17.00 and 18.00 h. There were only 2 significant effects of pinealectomy on these daytime values, one of which was a reduction in the elevation of Prl at 17.30 h. There were also more frequent very low values, less than 5 ng/ml, after pinealectomy. At night there was greater variation of plasma Prl in sham-operated rats and in general the animals showed a sudden elevation just prior to the time the lights were turned on. The values remained elevated for some time thereafter. After pinealectomy the elevation when the lights were turned on was slightly delayed and the responses were smaller in magnitude or even absent. There were significantly more high Prl values in the controls than in the pinealectomized animals in darkness and the area under the curve of Prl release, which was greater at night than in the daytime, was significantly lowered by pinealectomy.

Animals↗

Acute and chronic responses to iodine deficiency in rats.

Various indices of thyroid function were measured in rats at early (2 to 26 days) and at late (up to 55 weeks) intervals after the onset of an iodine deficient diet (LID). Control groups received the same diet with iodine-supplemented drinking water. The measurements included: thyroid total 127I concentration, thyroid weight, [131i] mit/[131i]dit and [131i]t3/[131i]t4 after a labeling period of 18--24 h, serum T4, serum T3, and serum TSH. In the acute experiments serum T4 was significantly decreased at 6--7 days. Thereafter, the decrease was rapid and progressive, and by 26 days serum T4 was reduced to undetectable levels (less than .05 mug per 100 ml). Thyroid T4 decreased more rapidly than serum T4, suggesting that the turnover rate of thyroid T4 increased soon after the onset of LID. Serum T3, in contrast to serum T4 showed no significant change during the 26 day period. Thyroid T3 decreased less rapidly than thyroid T4, but was greatly reduced by 26 days. Presumably the turnover rate of thyroih was slightly but significantly elevated at 4 days, before there was any detectable decrease in serum T4. Thereafter, the results were somewhat variable, but there appeared to be no significant further rise in serum TSH up to about day 15, despite the observation that serum T4 fell rapidly during this period. Only after 15 days did serum TSH display a sharp increase. It is apparent from these results that there is no simple inverse relationship between plasma T4 and plasma TSH. In the chronic experiments serum T4 remained undetectable. Serum T3 was decreased to about 50% of the normal level at 7 weeks but there appeared to be no further decrease even at 55 weeks. Serum TSH rose to very high levels at 12 weeks but showed no further increase thereafter. Thyroid 127I concentration reached its lowest value at 15 weeks and showed no further decrease. Thyroid weight, on the other hand, appeared to increase progressively. To evaluate the effect of severe iodine deficiency on thyroid status, rats that had been on LID for 3-4 months were exposed to a cold environment (4--5 C). Body temperature and survival rates were compared with those of matched controls receiving LID + KI drinking water. The body temperatures of the latter group increased significantly on exposure to cold, and all animals survived. On the other hand, the body temperature of rats on LID alone began to decrease about 5 days after the onset of cold exposure, and when the diet was sufficiently low in iodine the majority of the rats died within 15 days. These results suggest that thyroid function in severely iodine deficient rats is not adequate to meet the challenge of acute cold stress. In this sense, therefore, these animals may be daid to display signs of hypothyroidism.

Acute Disease↗

On the role of the central noradrenergic and dopaminergic systems in the regulation of TSH secretion in the rat.

Systemic administration of drugs affecting central noradrenergic and dopaminergic systems was used to evaluate their role in the regulation of TSH secretion in the rat. Alpha-methyl-p-tyrosine (alpha-MT) caused a depletion of brain norepinephrine and dopamine and a gradual decrease of serum TSH levels. Specific inhibitors of dopamine-beta-hydroxylase, diethyldithiocarbamate (DDC) and FLA 63, depleted central norepinephrine only and led to a simultaneous striking decrease of serum TSH. Blockade of alpha adrenergic receptors with phenoxybenzamine, but not with phentolamine, also depressed serum TSH. Blockade of beta receptors with propranolol had no effect. In contrast, the centrally and peripherally acting alpha receptor agonist, clonidine, increased serum TSH, whereas the peripherally acting methoxamine caused a decrease, probably due to non specific stress effect. A dose-related rapid inhibition of TSH secretion was observed following stimulation of dopamine receptors with apomorphine. Injection of L-Dopa had a similar effect. Blockade of the dopamine receptors with pimozide did not alter serum TSH, while blockade with spiroperidol led to a slight increase. The cold-induced surgeof TSH was abolished by pretreatment with DDC or phenoxybenzamine, reduced by apomorphine, but unaffected by pimozide or propranolol. The pituitary responsiveness to exogenous TRH was unaffected by administration of DDC or apomorphine. On the basis of these results, it is assumed that the central noradrenergic system has a stimulatory effect on the release of TRH from the hypothalamus, reflected in our experiments by the changes of serum TSH levels. It probably provides the drive for the tonic release of TRH in resting conditions and stimuli for the enhanced secretion during cold exposure. The effect is probably mediated by a central alpha-adrenergic mechanism. Activation of the dopaminergic system is inhibitory, but the physiological role of this effect remains to be established.

Animals↗

Localization of hypophysiotropic neurohormones by assay of sections from various brain areas.

The results of studies of the localization of the hypothalamic hypophysiotropic factors based on their direct determination in sections or nuclear punches are described. Luteinizing hormone-releasing hormone was found in high concentrations in the median eminence-arcuate nucleus complex, in lower concentrations in the mediobasal zone of the preoptic area. In addition to these hypothalamic sites, it is present in all four periventricular organs, especially in the organum vasculosum laminae terminalis. Thyrotropin releasing hormone has a widespread distribution. High concentrations are in the median eminence, arcuate nucleus, dorsomedial nucleus, and anterior part of the ventromedial nucleus. Lower concentrations are in several other structures of the hypothalamus, preoptic area and septum, and low but measurable quantities are found in most of the structures of the brain. Somatostatin is also present in most structures of the central nervous system, with highest concentrations in the median eminence, arcuate nucleus, ventromedial nucleus and periventricular nucleus. There are indications that the ventromedial nucleus or its immediate vicinity contains growth hormone releasing factor. Prolactin releasing activity was present in the median eminence and mediobasal parts of the anterior hypothalamus, whereas prolactin inhibitory activity was in the dorsolateral parts of the anterior hypothalamus and/or preoptic area.

Animals↗

Developmental patterns of plasma and pituitary TSH and prolactin and hypothalamic TRH in the female rat.

In developing female rats, pituitary content and concentration of TSH and prolactin measured twice daily (1000 and 1600 h) were low during the first two weeks of life and increased markedly between day 15 and 30. AM-PM variations in pituitary levels of both hormones were apparent, particularly during this latter phase of development. Plasma TSH levels increased between days 5 and 12, showing peak values at this age. After day 15, levels declined gradually to reach a nadir shortly before puberty. At puberty, plasma TSH remained low, showing only minor fluctuations. No consistent AM-PM differences in plasma TSH were observed at any age studied. Plasma prolactin was low between day 5 and 15, increasing thereafter. Starting at day 10, AM-PM fluctuations in plasma levels were detected, titers being higher in the afternoon than in the mornings. It has already been reported (Endocrinology 98: 630, 1976) that during puberty this pattern becomes more evident, peak values being reached in the afternoon of the first proestrus. Hypothalamic TRH content increased between day 5 and 15, reaching a maximum at this age and declining thereafter to adult values. No qualitative changes in pituitary TSH during development were observed, as determined by exclusion chromatography. The existence of divergent patterns of plasma TSH and prolactin during female sexual maturation and the fact that hypothalamic TRH titers than with prolactin levels suggest that the mechanism(s) that stimulates pituitary release of these two hormones during sexual development is different.

Animals↗

Mechanism of the effects of hypothalamic deafferentation on prolactin secretion in the rat.

Male rats with complete hypothalamic deafferentation had consistently lower serums prolactin concentrations than controls when the blood samples were obtained under other anesthesia. However, when rats were decapitated, both groups had similar low prolactin levels. Posterolateral deafferentation was as effective as complete deafferentation in preventing the stress-induced prolactin release, whereas anterior frontal deafferentation had only a small effect, L-Dopa (100 mg/kg body wt, ip) decreased prolactin titers in both control and deafferented animals, whereas reserpine (1 mg/kg body wt, ip) had the opposite effect. Since both drugs inhibited prolactin release from pituitaries in vitro, the decrease of prolactin levels following L-dopa in vivo might have been caused not only by stimulation of PIF release but also at least partly by the direct effect of the drug on the pituitary. However, the increase of serum prolactin following reserpine was in all probability caused by inhibition of PIF secretion. Electrolytic lesions in the median eminence of deafferented rats caused an elevation of serum prolactin which was more marked in female than in male rats. On the contrary, deafferentation in the females affected prolactin levels less than in males. It is concluded that hypothalamic deafferentation prevents ether-induced release of prolactin and that the "low" levels of the deafferented animals are probably due to a tonic release of prolactin-inhibiting factor (PIF) from the isolated island. It is though that this continuous release of PIF might be maintained by persisting autonomous activity of the adrenergic, presumably dopaminergic, neurons contained in the isolated island.

Animals↗

Localization of luteinizing hormone-releasing hormone in the preoptic area and hypothalamus of the rat using radioimmunoassay.

To determine the localization of luteinizing hormone-releasing hormone (LHRH), five brains from adult male rats were serially sectioned in a cryostat at - 10 C in either the frontal, horizontal or sagittal planes. Acetic acid-ethanol extracts of each section were assayed for LHRH using radioimmunoassay (RIA) and in some cases using bioassay as well. Approximately 0.2 ng LHRH was concentrated in medial basal preoptic (MB-PO) tissue overlying the rostral portion of the optic chiasm. This LHRH appears to be associated with the organum vasculosum of the lamina terminalis and/or adjacent neural tissue. Uniform, low levels of LHRH were detected in hypothalamic tissue between the preoptic area (POA) and arcuate-median eminence (ARC-ME) region. In the ARC-ME region 2.7 ng of LHRH were concentrated primarily in the median eminence. The lateral distribution of LHRH in the ARC-ME region extended beyond the median eminence into tissue corresponding to the lateral aspect of the ventromedial nucleus. Concomitant bioassay and RIA determinations of LHRH were highly correlated. Of the sections bioassayed, only those sections containing LHRH released FSH. These results confirm the presence of LHRH in the POA and in the rostral hypothalamus of the rat brain. The possible significance of LHRH in the POA for the regulation of LH release is discussed.

Animals↗

Effect of acute exposure to cold on the activity of the hypothalamic-pituitary-thyroid system.

The effects of a sudden but sustained exposure to cold (1 to 6C) on serum TSH, thyroxine (T4) and triiodothyronine (T3) (all measured by radioimmunoassay), pituitary TSH concentration, pituitary TSH secretory responsiveness to hypothalamic extract or synthetic thyrotropin-releasing hormone (TRH) in vitro as well as in vivo, and the changes of the thyrotropin-releasing activity in three TRF-rich hypothalamic areas were determined. In normal animals, serum TSH underwent a series of oscillations, first rising then returning to the basal levels, then rising again, whereas serum T4 and T3 increased within 2 h of cold exposure and remained elevated. Pituitary TSH concentration and the in vitro pituitary responsiveness declined after an initial elevation, whereas the in vivo responsiveness to TRH was diminished throughout the whole exposure to cold. Thyroid-blocked animals with steady, low levels of serum T4 and T3 showed a step by step increase of serum TSH levels and no changes in the other parameters. It is therefore assumed that the decrease of TSH secretion following the initial rise is due to a feedback inhibition by the increased levels of thyroid hormones as is the decreased pituitary responsiveness of TRH in vivo. The pituitary responsiveness in vitro seems to be determined by TSH pituitary concentrations, the changes of which are probably also secondary to the changes of the thyroid hormone levels. The mechanism of the second rise of serum TSH levels is not clear. Thyrotropin-releasing factor (TRF) activity was higher after 2 and 24 h of cold exposure in the median eminence and after 8 h in the anterior hypothalamus-preoptic area, but lower after 8 and 24 h in the dorsomedial hypothalamus. Since the changes of TRF activity in the median eminence coincided with the elevated serum TSH, they are assumed to reflect increased TRF production and secretion. The significance of the TRF changes in the other two areas is not clear.

Adrenalectomy↗