Search PubMed⌕ Search

Biomedical subjects

L Krulich

Publications and source records attributed to L Krulich.

At least 37 records · Page 2Linked to original sources
PubMed1982

On the prolactin-inhibiting effect of neurotensin. The role of dopamine.

Neurotensin (NT) when injected in a dose of 5 micrograms into the third cerebral ventricle of conscious, unrestrained male rats, outfitted with chronic third ventricle and jugular cannulae, decreased the resting prolactin (PRL) levels. NT (5 micrograms) also markedly inhibited the PRL-releasing effect of activation of central serotonin receptors by 5-hydroxytryptophan (5HTP, 15 mg/kg) in animals pretreated with fluoxetine (4 mg/kg). however, interruption of dopamine (DA) neurotransmission by either alpha-methyl-p-tyrosine (alpha MT, 250 mg/kg) or spiroperidol (0.3 mg/kg) led to a blockade of the PRL-inhibiting effect of NT. Treatment of animal with alpha MT prior to the injection of fluoxetine and 5HTP also blocked the PRL-inhibiting effect of NT. These results suggest that the central dopaminergic system mediates the PRL-inhibitory effect of NT.

Animals↗
PubMed1981

TRH in the rat cerebellum: I. Distribution and concentration.

We determined the regional distribution and concentration of endogenous TRH in the rat cerebellum. Radioimmunoassay of endogenous TRH extracted and purified from five different regions of the rat cerebellum and whole hypothalamus showed that the cerebellar vermis contained 24 pg/mg, the hemispheres 74 pg/mg, the deep cerebellar nuclei 148 pg/mg, and the flocculo-nodular region 559 pg/mg of TRH. The highest concentration of TRH was in the cerebellar paraflocculi, which contained 786 pg/mg. The hypothalamic concentration of TRH was 465 pg/mg. Assay of the non-purified tissue fractions (crude extracts) resulted in lower TRH values in accordance with data previously reported by other authors. Bioassay analysis of TRH in purified fractions resulted in values similar to those obtained by radioimmunoassay. On the basis of these findings we hypothesize a functional role for TRH in the cerebellum.

Animals↗
PubMed1981

TSH release during the estrous cycle of the rat: variations in responsiveness to cervicovaginal stimulation.

Serum TSH, LH and FSH were measured at various times during the day, during the estrous cycle of the rat. Proestrous surges of FSH and LH were detected as previously reported. TSH values fell to low levels in the late afternoon on each day of the cycle. There was a significant elevation of TSH at 13.00 h on both proestrus and estrus. The elevation of TSH on proestrus was accompanied by a significant fall in pituitary TSH stores. LH stores were also significantly depleted by 19.00 h on proestrus. Cervicovaginal stimulation by a glass rod provoked a significant rise in serum TSH 3 h after stimulation at 10.00 h on estrus but not on other days of the cycle. Responsiveness to a test dose of TRH varied during the cycle. It was maximal on proestrus and declined to minimum values on diestrus day II. Values were further lowered after ovariectomy but were restored to diestrus day II levels by treatment with estradiol. It is concluded that there are important cyclic variations in TSH release in the female rat, that cervicovaginal stimulation can provoke TSH release on estrus and that these changes are associated with altered responsiveness to TRH. We conclude that ovarian steroids modulate the release of TSH from the pituitary and affect the responsiveness to cervicovaginal stimulation. These changes are presumably brought about by alterations in TRH release and in responsiveness of the pituitary to the neurohormone.

Animals↗
PubMed1981

On the mode of the prolactin release-inhibiting action of the serotonin receptor blockers metergoline, methysergide, and cyproheptadine.

Using animals with large electrolytic lesions of the median eminence-mediobasal hypothalamus, we confirmed earlier findings that metergoline (ME) and methysergide (MS) inhibit PRL secretion through activation of the dopamine receptors of the pituitary lactotrophs and established, in a quantitative manner, that their dopaminergic potencies are comparable to the potency of the dopamine receptor agonist, piribedil, with ED50 in the order of 0.35 to 0.22 mg/kg. Cyproheptadine (CYP), acting by an unknown mechanism, had only a weak inhibiting effect (ED50 greater than 20.0 mg/kg) in these experimental conditions. In the second part of the study, the PRL-inhibiting actions of ME, MS, CYP, and piribedil, respectively, were tested against the PRL release-stimulating effect of activation of the central serotonergic system that was induced by administration of a large dose of L-5-hydroxytryptophan (5HTP; 100 mg/kg), a small dose of 5HTP (15 mg/kg) in rats pretreated with fluoxetine, or by the serotonin receptor agonist quipazine (10.0 mg/kg, ip). The inhibiting potencies of ME (ED50 0.019, 0.014, and 0.048 mg/kg, respectively) against these three stimuli were much larger than in the lesioned animals or than the corresponding potencies of piribedil (ED50 2.2, 0.24, and 0.41 mg/kg, respectively). It is assumed that in these experimental conditions ME inhibited PRL release by blockade of the central serotonin receptors in addition to its dopaminergic effect and that at low doses (0.1 mg/kg or less) the entire inhibiting effect of ME was probably due to its antiserotonergic activity. With MS, which is a weaker serotonin receptor blocker than ME (ED50 0.178, 0.075, and 0.55 mg/kg, respectively, for the three serotonergic stimuli of PRL release), the antiserotonergic component in its PRL-inhibiting effect was evident but less clearly separable from the dopaminergic component in experiments with 5HTP and with fluoxetine plus 5HTP, whereas in experiments with quipazine the entire action could be accounted for by its dopaminergic activity. CYP was the least potent among the three blockers (ED50 0.6, 0.4, and 1.37 mg/kg, respectively, for the three serotonergic stimuli of PRL release), but appropriate tests indicated that it acted only as a serotonin receptor blocker and not by virtue of its antihistaminic, anticholinergic properties or by a direct action on the pituitary lactotrophs. SQ 10,631, another serotonin receptor blocker that was also tested, had no PRL-inhibiting activity. Because of the dual nature of the PRL-inhibiting mechanism of ME and MS and the low effectiveness of CYP, combined possibly with other actions, the serotonin receptor blockers have limited value in studies concerning the role of the central serotonergic system in the regulation of PRL secretion.

Animals↗
PubMed1981

Elevation of serum 3,5,3'-triiodothyronine and thyroxine levels in rats fed Remington diets; opposing effects of nutritional deficiency and iodine deficiency.

In the course of experiments on iodine deficiency induced by Remington diets in rats, we observed that the Remington diet supplied by ICN Nutritional Laboratories, though very deficient in iodine (less than 20 micrograms I/kg), did not lead to the rapid loss of thyroid iodine and the rapid decrease in serum T4 expected on the basis of previous studies with a similarly iodine-deficient Remington diet from another source. In searching for an explanation for this observation, we noted that the ICN Remington diet was nutritionally much more deficient than Remington diets from other suppliers. We also noted that when rats were placed on the iodide-supplemented ICN Remington diet there was a marked increase in serum T3 and T4. In one experiment, rats receiving the ICN Remington diet plus KI in the drinking water for 16 days showed a serum T3 level of 109 +/- 16 ng/dl and a serum T4 level of 6.6 micrograms/dl compared to 52 +/- 7.8 and 4.4 +/- 0.8, respectively, in control rats on a stock diet. These elevations were not simply the result of increased binding to serum proteins. Serum protein-binding studies by the method of equilibrium dialysis showed a very slight decrease in the percent dialyzable fraction for T3 and T4. However, calculated free T3 levels were significantly elevated (P less than 0.001), and increases in free T4, though less striking, were also significant. These elevations were not accompanied by evidence of hyperthyroidism, as judged by measurements of O2 consumption or serum TSH. Although the specific nutritional factors and mechanisms have not yet been defined, our studies demonstrate that nutritional deficiencies in a Remington diet may act to oppose the effects of the iodine deficiency itself. Our observation that the iodide-supplemented ICN Remington diet has a marked serum T3- and T4-elevating effect offers a possible explanation for the blunted thyroidal responses of rats to the same diet lacking added iodide. Our studies also suggest that alteration of peripheral T4 and T3 conversion may not be the only mechanism by which nutritional factors affect serum T3 and T4 levels.

Animals↗
PubMed1981

Strain differences among rats in response to Remington iodine-deficient diets.

Male rats of five different strains (Simonsen albino, Wistar, Long-Evans, Holtzman Sprague-Dawley, and Charles River Sprague-Dawley) were tested for their response to the U.S. Biochemical Corp. Remington low iodine diet containing 15-18 microgram I/kg. Measurements made after the diet had been fed for 28-30 days indicated that Simonsen albino and Wistar strains consistently showed the greatest response, based on degree of thyroid enlargement, depletion of thyroidal iodine, reduction in serum T4, and elevation of serum TSH. Long-Evans and Holtzman Sprague-Dawley rats responded relatively poorly to the low iodine diet. One experiment included female rats, and the limited data suggested that within a given strain there was no significant sex difference. With more prolonged feeding (84 days), the difference between a rapidly responding strain (Simonsen albino) and a more slowly responding strain (Holtzman Sprague-Dawley) was not so marked. Our results indicate that given sufficient time and a diet sufficiently low in iodine, even a more slowly responding strain will ultimately develop signs of extreme iodine deficiency. However, it is inconvenient and expensive to maintain rats on a Remington low iodine diet for 3 months, and studies on the effect of severe iodine deficiency are much more rapidly performed using a rapidly responding strain such as the Simonsen albino. Our observation that rats of different strains differ markedly in their responses to an iodine-deficient diet suggests that hereditary factors play an important role in this response.

Animals↗
PubMed1981

Hypothyroidism in severely iodine-deficient rats.

The thyroid status of severely iodine-deficient rats was assessed by measurement of the resting metabolic rate (RMR) and liver mitochondrial alpha-glycerophosphate dehydrogenase (alpha-GPD). Rats maintained on the iodine-deficient diet for 2 or 3 months showed significantly reduced RMR and alpha-GPD, compared to rats on the same diet supplemented with KI in the drinking water. They also displayed markedly reduced serum T4 levels, slightly reduced serum T3 levels, and highly elevated serum TSH levels. A significant decrease in liver alpha-GPD was observed 29 days after the rats were placed in iodine-deficient diet. However, the decrease in RMR in the same animals was not statistically significant. These results suggest that measurement of liver alpha-GPD may be a more sensitive index of impending hypothyroidism than measurement of O2 consumption. The present study demonstrates that a hypothyroid state can be induced in rats exposed to a severely iodine-deficient diet. In severe iodine deficiency, the compensatory mechanisms of increased TSH stimulation and preferential T3 secretion from the thyroid are insufficient to prevent a fall in serum T3. The hypothyroid state results from the inability to maintain a normal serum T3 level and possibly also from the very low levels of serum T4.

Animals↗
PubMed1980

Role of central nervous system neurotransmitters in mediating the effects of morphine on growth hormone- and prolactin-secretion in the rat.

Unanesthetized adult male rats with indwelling right atrial cannulae were used in the majority of experiments. Morphine (MOR, 3.0 mg/kg) caused a large but transient increase in both GH and PRL levels, which could be prevented with naloxone. Disruption of central noradrenergic function with diethyldithiocarbamate (400 mg/kg) or phenoxybenzamine (15 mg/kg) abolished the GH-releasing effect of MOR, without interfering with the PRL secretory response. Depletion of brain serotonin stores with p-chlorophenylalanine (300 mg/kg) or 5,7-dihydroxytryptamine or administration of serotonin receptor blocker, cyproheptadine (2.5 mg/kg), did not diminish the GH respnse to MOR but it inhibited, or in the case of 5,7-DHT treatment abolished the activation of PRL secretion. Additionally, metergoline (0.1 and 1.0 mg/kg), another serotonin receptor blocker, caused an inhibition of the GH-releasing action of MOR; however, this inhibition was reversed by pretreatment with spiroperidol (0.1 mg/kg). Metergoline also markedly diminished the MOR-induced elevation of PRL. Inhibition of catecholamine synthesis with alpha-methyl-p-tyrosine (alpha-MT, 250 mg/kg) blunted the effect of MOR on GH; however, dopamine receptor blockers, spiroperidol (0.01 and 0.1 mg/kg) or (+)butaclamol (0.3 and 1.3 mg/kg), were without any influence. alpha-MT or spiroperidol did not alter the effect of MOR on PRL secretion, but the higher dose of (+)butaclamol suppressed it. It is concluded that the GH-releasing action of MOR requires unimpaired functioning of the central noradrenergic system, while the serotonergic and dopaminergic systems appear to play no significant role in it. In contrast, serotonergic systems seem to be essential for the activation of PRL secretion, whereas the noradrenergic system is not involved. It remains uncertain whether morphine activtes PRL secretion also through inhibition of dopaminergic activity. We favor the view that the dopaminergic component participates in the PRL activation by MOR, but that its contribution to the overall effect is rather small.

Animals↗
PubMed1980

Lack of evidence that the central serotoninergic system plays a role in the activation of prolactin secretion following inhibition of dopamine synthesis or blockade of dopamine receptors in the male rat.

Administration of alpha MT to inhibit catecholamine synthesis or dopamine (DA) receptor blockade with spiroperidol had no effect on the hypothalamic concentration of 5HT or 5HIAA. Fluoxetine to block serotonin uptake had no influence on the elevation of serum prolactin levels induced by alpha MT or DA receptor blockers and conversely alpha MT did not influence the prolactin-releasing action of 5HTP alone or in combination with fluoxetine. Depletion of brain serotonin stores with p-chlorophenylalanine did not affect the prolactin-releasing action of alpha MT or DA receptor blockers. In contrast, the serotonin blocker methysergide, but not cyproheptadine, inhibited the prolactin-releasing effect of alpha MT or alpha-flupentixol, a DA receptor blocker, but not of spiroperidol, another DA receptor blocker. The intensity of the inhibition induced by methysergide paralleled the intensity of inhibition induced by apomorphine. Methysergide conspicuously lowered serum prolactin in animals with electrolytic destruction of the median eminence, whereas cyproheptadine had only a slight effect. The prolactin-inhibiting effect of methysergide could be prevented by pretreatment of the lesioned rats with spiroperidol. It is concluded (1) that elimination of the influence of the DA system does not activate the central serotoninergic system; (2) that activity of the serotoninergic system has no role in the activation of prolactin secretion induced by suppression of the inhibitory dopaminergic influence, and (3) that the inhibiting action of methysergide on the prolactin-releasing effect of alpha MT or alpha-flupentixol is due to its dopamine receptor agonist activity rather than to blockade of serotonin receptors.

5-Hydroxytryptophan↗
PubMed1980

Effect of triiodothyronine injection on levels of triiodothyronine and thyroid-stimulating hormone in sera and milk of lactating rats and in sera of their sucklings; precocious development of jejunal alpha-disaccharidases in the sucklings.

Administration of high doses of triiodothyronine (T3) for 4 days to lactating rats evokes an increase in T3 levels in their sera and milk, as well as in the sera of pups suckled by them. Thyroid-stimulating hormone levels in sera of mothers and sucklings are decreased. Suckling rats of T3-treated mothers exhibit a precocious increase in the activity of jejunal sucrase and maltase as well as in activity of several liver acid beta-glycosidases.

Acetylglucosaminidase↗