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L Krulich

Publications and source records attributed to L Krulich.

At least 19 recordsLinked to original sources
PubMed1990

Interaction between norepinephrine and serotonin in the neuroendocrine control of growth hormone release in the rat.

Both alpha 2-adrenergic (alpha 2) and serotonergic (5HT) neurons are associated with stimulation of GH secretion via GRH release. The object of this study was to determine whether the 5HT system is involved in the stimulation of GH secretion by alpha 2-receptor agonists. There are two parts of this study. In the first, the relationship between alpha 2-5HT systems were analyzed by determining if alpha 2-stimulated GH release is mediated by 5HT. In this model, systemically administered alpha 2-agonists [clonidine (CLON) or UK14,304] were tested against 5HT antagonists (meterogoline or cyproheptadine) or 5HT synthesis inhibitors (p-chlorophenylalanine methylester hydrochloride). In the second, sites of 5HT-GRH interaction were determined by testing the response to CLON after 5HT neurotoxin [5,7-dihydroxytryptamine (5,7-DHT)] microinjection at specific hypothalamic nuclei. In both experiments sequential blood samples were withdrawn from silastic jugular cannulas in unanesthetized, freely moving animals. Metergoline (0.045 and 0.135 mg/kg, iv) and cyproheptadine (0.969 micrograms/kg, iv) suppressed, in a dose-dependent manner, the CLON (33 or 66 micrograms/kg, iv)-induced GH surge that was detected 15-30 min after injection in control animals. Both cyproheptadine (0.969 micrograms/kg, iv) and p-chlorophenylalanine (300 mg/kg, ip) effectively suppressed the UK14,304 (220 micrograms/kg, iv)-induced GH surge that occurred 15-30 min after injection in control animals. These data suggest that an intact 5HT system is required for alpha 2-stimulated GH release. 5,7-DHT neurotoxin microinjected into the midline arcuate nucleus (6 micrograms/mg,iv) or bilaterally into the ventromedial nucleus or perifornical area (4 micrograms/0.2 microliter) 5 days previously suppressed the CLON (30 micrograms/kg)-induced GH surge only in animals with arcurate nucleus lesions. To determine if the suppression was mediated by inhibition of GH-releasing hormone (GRH) or stimulation of somatostatin (SRIF), an additional experiment was conducted including 5,7-DHT arcuate nucleus-lesioned animals injected with anti-SRIF. Inasmuch as anti-SRIF failed to reverse the 5,7-DHT suppression of GH secretion, the results of this experiment suggest that GRH mediates NE-5HT-induced GH secretion. In conclusion, these data suggest that alpha 2 activation of GH secretion requires intact serotonergic terminals in the arcuate nucleus and most likely involves GRH rather than SRIF, release.

5,7-Dihydroxytryptamine↗
PubMed1989

Prolactin (PRL) release-inhibiting properties of the alpha 2 adrenergic receptor antagonist idazoxan: comparison with yohimbine.

The effects of the alpha 2 adrenergic receptor antagonists yohimbine (YOH) and Idazoxan (ID) on secretion of PRL were compared in nonanesthetized male rats bearing permanent intraatrial cannulae for i.v. drug delivery and serial blood sampling. YOH induced a dose-related elevation of basal plasma PRL levels. ID had either no effect or a tendency to lower them and effectively inhibited stimulation of PRL secretion with morphine, 5-hydroxytryptophan (5HTP), quipazine or restraint stress. YOH at low doses did not alter the PRL secretory responses to these stimuli or enhanced them at the highest dose used (1.56 mg/kg). ID inhibited the PRL-stimulating, effect of 5HTP or morphine following inhibition of NE synthesis with FLA63 or pretreatment with clonidine. It also blocked the effect of quipazine in rats pretreated with prazosin. It is concluded that ID, in a complete contrast to YOH effectively inhibits PRL secretion. The inhibitory mechanism appears to be unrelated to its interaction with the alpha adrenergic receptors.

5-Hydroxytryptophan↗
PubMed1989

The paradox of alpha 2 adrenergic regulation of prolactin (PRL) secretion. I. The PRL-releasing action of the alpha 2 receptor agonists.

Systemic (IV) administration of the alpha 2 receptor agonist clonidine is known to stimulate secretion of PRL and growth hormone (GH) suggesting a stimulatory role of the central alpha 2 receptors in the regulation of the two hormones. The present work confirms this notion for GH but indicates that the alpha 2 agonists stimulate PRL release by a peripheral action not involving central alpha 2 receptors. This conclusion is based on the following findings: 1) The minimum effective IV dose of clonidine or UK 14304 was four times larger for activation of PRL than GH secretion and had already manifest extracentral effects (elevation of arterial BP). 2) Subcutaneous injection of UK 14304 (220 micrograms/kg) elevated plasma GH but not PRL levels indicating that an effective activation of the central alpha 2 receptors does not stimulate PRL release. 3) Peripherally acting alpha 2 agonists (p-aminoclonidine, oxymetazoline) had no effect on GH secretion but stimulated PRL release in a manner identical with the effect of clonidine or UK 14304. 4) The peripherally acting alpha 2 antagonist DG-5128 blocked only the PRL secretory response to UK 14304 whereas the peripherally and centrally active yohimbine blocked the PRL and GH responses.

Adrenergic alpha-Agonists↗
PubMed1989

The paradox of alpha 2 adrenergic regulation of prolactin (PRL) secretion. II. PRL-releasing action of the alpha 2 receptor antagonists.

It has been suggested that the stimulation of the secretion of PRL by the alpha 2 adrenergic receptor antagonists (yohimbine, piperoxane) results from blockade of an inhibitory influence imposed on PRL release by the central alpha 2 receptors (7, 15). Our present results do not support these conclusions for the following reasons: 1) The effectiveness of the alpha 2 receptor antagonists yohimbine (YOH), rauwolscine (RAU), Wy 26392 and idazoxan (IDAZ) respectively to activate secretion of PRL was not related to their alpha 2 antagonist potencies. RAU was more effective in activation of PRL secretion than either YOH or Wy 26392 although it had a similar alpha 2 antagonist activity, while IDAZ, the most potent alpha 2 blocker among the four compounds, did not stimulate PRL secretion. 2) The PRL-releasing effect of YOH or Wy 26392 was reversed by the alpha 2 agonist clonidine but the same effect of RAU was not, speaking against a common alpha 2-mediated mechanism of action of the three antagonists. 3) The PRL-stimulating effect of YOH, RAU or Wy 26392 persisted following inhibition of NE synthesis and presumably release with FLA 63, DDC or combination of reserpine and DDC. 4) Conversely, we found no indication for an inhibiting influence of activation of the alpha 2 receptors on the secretion of PRL. We conclude that the stimulation of PRL secretion by the alpha 2 receptor antagonists is not derived from blockade of the central alpha 2 receptors but from other, not yet defined properties of the drugs.

Adrenergic alpha-Antagonists↗
PubMed1989

Evaluation and characterization of the hyt/hyt hypothyroid mouse. II. Abnormalities of TSH and the thyroid gland.

The hyt/hyt mouse (BALB/cBY-hyt, C.hytRF) provides a useful model for exploring the effect of inherited severe primary hypothyroidism. Studies were undertaken to try to define the basis of the primary hypothyroidism in mice homozygous for the autosomal recessive gene, hyt. These mice had congenital hypothyroidism of fetal onset after 15 days post conception. Through their lifetime, the hyt/hyt mice had reduced serum thyroxine (T4), triiodothyronine (T3), reduced thyroid gland intralumenal colloid on electron microscopy and a 100-fold elevation of TSH-like activity compared to hyt/+ littermates. Thyroglobulin made in hyt/hyt animals was similar in size to normal thyroglobulin which was inconsistent with a major structural thyroglobulin gene defect. The thyroglobulin was iodinated. Marked, erratic dilation of rough endoplasmic reticulum (RER) was noted in hyt/hyt mouse follicular cells. Despite these ultrastructural findings, pulse chase and immunoprecipitation studies with isolated hyt/hyt and normal thyroid glands indicated that normal thyroglobulin processing occurred in the RER and Golgi of the hyt/hyt mice. The hyt/hyt thyroid glands were hypoplastic compared to hyt/+ littermates. Histologically, the hyt/hyt thyroid glands demonstrated an increase in smaller follicular cells, and greater variability in follicular size compared to hyt/+ littermates. Histological and ultrastructural abnormalities in the gland were similar to those seen in certain cases of human congenital hypothyroidism with TSH receptor insensitivity of the thyroid gland. These findings along with the significant TSH elevation, the reduction in colloid and in serum T3 and T4, the efficacy of the hypothalamo-pituitary-thyroid feedback system, and previous observations of reduced iodine uptake and intrathyroidal T4, suggested that primary hypothyroidism in the hyt/hyt mouse might be due to a defect in TSH responsivity of the thyroid gland.

Animals↗
PubMed1986

Opioid kappa receptors and the secretion of prolactin (PRL) and growth hormone (GH) in the rat. I. Effects of opioid kappa receptor agonists bremazocine and U-50,488 on secretion of PRL and GH: comparison with morphine.

The effects of bremazocine and U-50,488, two selective opioid kappa receptor agonists, and the preferential mu receptor agonist morphine on the secretion of PRL and GH were compared in conscious male rats bearing permanent right atrial cannulae for serial blood sampling and drug delivery. All three opioids stimulated PRL secretion in a dose-related manner, but the kappa agonists differed from morphine in several respects. They were considerably more potent than morphine in triggering a PRL response, but were unable to elevate PRL levels to more than 100 ng/ml, whereas morphine, at the highest dose (4.5 mg/kg), induced an almost twice larger response. Also their PRL-releasing effect was inhibited more strongly by the preferential kappa receptor antagonist Mr-2266 than by naloxone, whereas Mr-2266 and naloxone, which are equipotent as antagonists of the mu receptors, were equipotent in suppressing the PRL-stimulating effect of morphine, a mu agonist. In a complete contrast to morphine, which effectively stimulated GH secretion, the kappa agonists had no effect on GH release at lower doses and suppressed it at higher doses. It is concluded that the PRL-releasing effect of the kappa agonists is mediated by the kappa receptors which may participate with the mu receptors in regulation of PRL secretion by opioids. The GH-inhibiting effect of the kappa agonists requires further clarification.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1986

Opioid kappa receptors and the secretion of prolactin (PRL) and growth hormone (GH) in the rat. II. GH and PRL release-inhibiting effects of the opioid kappa receptor agonists bremazocine and U-50,488.

An analysis of the GH release-inhibiting action of the opioid kappa receptor agonists bremazocine and U-50,488, established earlier, was attempted by testing the agonists against activation of GH secretion by morphine or clonidine in male rats bearing right atrial cannulae for serial blood sampling and drug delivery. Both kappa agonists inhibited the effect of subsequent administration of clonidine in a dose-related manner. Bremazocine was approximately ten times more potent than U-50,488, a ratio corresponding to the known affinities of the two compounds for the kappa receptors. The inhibiting action of bremazocine was more strongly reversed by the preferential kappa receptor antagonist Mr-2266 than by naloxone, neither of which interfered with the GH-stimulating effect of clonidine. Bremazocine, however, did not alter the activation of GH secretion by exogenous growth hormone releasing factor. Thus, the inhibiting effect of bremazocine and probably U-50,488 seems to be derived from stimulation of the kappa receptors which in turn activates a GH release inhibiting mechanism of unknown identify which, however, does not involve release of somatostatin. Both kappa agonists also inhibited the effect of morphine, but in this case U-50,488 was approximately hundred times less effective than bremazocine. Since bremazocine and U-50,488 are antagonists of the delta receptors, which seem to mediate the GH-releasing effect to morphine, their inhibiting effect in this instance may be related to this property rather than to an action on the kappa receptors. Bremazocine, but not U-50,488, was also highly effective in inhibiting stimulation of PRL secretion by morphine.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1985

Possible delta receptor mediation of the effect of beta-endorphin on luteinizing hormone (LH) release, but not on prolactin (PRL) release, in the ovariectomized rat.

Administration of opioid receptor antagonists was utilized to determine the opioid receptor type involved in the suppression of LH release by beta-endorphin (beta-END). Long-term (three to four weeks) ovariectomized rats with chronic third ventricular cannulae were fitted with jugular catheters and received treatment with vehicle or one of three opioid antagonists. The delta antagonist ICI 154, 129, but not the mu1 or mu antagonists naloxazone or beta-funaltrexamine, respectively, blocked the suppressive effect of beta-END on plasma LH levels and transiently but significantly increased LH levels above preinfusion value. None of the antagonists significantly reduced the beta-END-induced release of PRL. These results provide evidence that the inhibitory effect of beta-END on LH release may be mediated by delta receptors.

Animals↗
PubMed1985

On the mechanism of growth hormone autofeedback regulation: possible role of somatostatin and growth hormone-releasing factor.

To determine the role of somatostatin (SRIF) and GH-releasing factor (GRF) in GH autofeedback, 20 micrograms rat GH in 2 microliter were injected into the third ventricle (IVT) 1 or 3 h before injection of the alpha 2-receptor stimulator clonidine (50 micrograms/kg, iv), which elevates plasma GH and TSH levels in normal rats. GH preinjected 1 or 3 h before clonidine significantly suppressed the clonidine-induced GH surge, whereas TSH release was not affected by GH. Preinjection of ovine LH IVT following the same protocol did not inhibit the clonidine-induced GH surge, suggesting a specific effect of IVT GH. Passive immunization with 400 microliters sheep antisomatostatin serum did not reverse the inhibition of the clonidine-induced GH surge by exogenous GH administered IVT either 1 or 3 h before clonidine. The TSH response was augmented by this procedure. Furthermore, IVT GH did not reduce the surges of GH and TSH elicited by GRF (250 ng/kg, iv) and TRH (150 ng/kg, iv) administered 1 or 3 h after IVT rat GH. These results suggest that GH autofeedback is mediated by reduced GRF secretion, rather than enhanced SRIF release.

Animals↗
PubMed1978

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↗
PubMed1978

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↗