Biomedical subjects

L L Murphy

Publications and source records attributed to L L Murphy.

25 records · Page 2Linked to original sources

PubMed1988

Inhibition of suckling-induced milk ejections in the lactating rat by delta 9-tetrahydrocannabinol.

The effect of delta 9-tetrahydrocannabinol (THC) on suckling-induced oxytocin release was investigated by recording intramammary pressure changes in suckled rats treated iv with THC (0.5 mg/kg BW) or vehicle. Latency to the first posttreatment milk ejection and posttreatment milk ejection intervals and pressure wave amplitudes were compared between THC- and vehicle-treated rats. Before treatment, intervals between milk ejections averaged 6.5 +/- 1.3 (+/- SE) and 7.0 +/- 0.7 min for vehicle- and THC-treated groups, respectively. Vehicle injections did not alter the frequency of milk ejections, which continued at an overall mean interval of 7.6 +/- 0.7 min after treatment. In contrast, THC treatment was followed by a transient suspension of milk ejections, with a latency of 59.3 +/- 7.4 min before the first posttreatment milk ejection was recorded (P less than 0.001). Intervals between subsequent ejections averaged 15.3 +/- 2.0 to 16.1 +/- 1.3 min and were lengthened relative to corresponding intervals in vehicle-treated animals (P less than 0.05). The amplitudes of pressure waves were not significantly affected by treatment. Oxytocin (0.5 mU) injections 10 or 30 min after THC treatment evoked abrupt increases in intramammary pressure, indicating continued responsiveness of the mammary gland to oxytocin stimulation. These data suggest that THC interferes with the release of oxytocin in response to suckling. To our knowledge, this provides the first evidence that THC inhibits posterior pituitary function.

Animals↗

PubMed1987

Selective modulation of FSH and LH secretion by steroids.

Significant divergence between the pattern of FSH and LH secretion has been observed in the ovulatory cycle, after ovariectomy and during puberty. The presence of an FSH-releasing factor, gonadal FSH inhibiting and releasing peptides and changes in the pulsatile pattern of LHRH secretion are among the postulates used to explain the divergent secretion of FSH and LH. Experiments in our laboratory have shown considerable evidence of differential regulation of FSH and LH secretion by steroids in the absence of gonadal regulatory peptides. Natural and synthetic estrogens show significant differences in the suppression of FSH and LH in the ovariectomized rat using a standard uterine response to the estrogen as the end point. In the immature ovariectomized rat treated with a low dose of estradiol that is sufficient for the synthesis of progesterone receptors to ensure progesterone sensitivity, but not large enough to induce estrogen triggered LH surges, progesterone administration resulted in a pattern of LH and FSH secretion similar to that observed on the day of proestrus in the cycling rat. Selective secretion of FSH was induced in the estrogen primed immature rat model by the administration of progesterone metabolite 5 alpha-dihydroporgesterone (5 alpha-DHP) while selective LH secretion was induced by 3 alpha, 5 alpha-tetrahydroprogesterone (3 alpha,5 alpha-THP). The selective secretion of FSH and LH induced by progesterone metabolites was confirmed in the immature female rat primed with PMSG and maintained in constant light. 5 alpha-DHP was also able to induce a greater release of FSH when administered to the adult cycling rat on proestrus. The priming of the pituitary gonadotrope in secreting a high baseline level of FSH or responding to LHRH in releasing a greater amount of FSH appeared to be an important factor in selective FSH release and such priming can be brought about by 5 alpha-DHP in the absence of gonadal regulatory peptides.

Animals↗

PubMed1986

Induction of luteinizing hormone release by electrochemical stimulation of the medial preoptic area in delta 9-tetrahydrocannabinol-blocked proestrous rats.

The predominant psychoactive constituent of marijuana, delta 9-tetrahydrocannabinol (THC), blocks the preovulatory luteinizing hormone (LH) surge and ovulation in rats treated with THC (10 mg/kg body weight) during the early afternoon of proestrus. When THC-blocked proestrous rats were subjected to unilateral electrochemical stimulation (100 microA anodal DC for 45 s) in the medial preoptic area (mPOA), serum LH was significantly elevated at 30, 60 and 90 min after stimulation in comparison with LH levels measured in sham-stimulated control animals at those times. The induced LH release was sufficient to elicit ovulatory responses comparable to the spontaneous ovulations observed in control rats treated only with the drug vehicle. These results are consistent with the hypothesis that THC inhibits gonadotropin secretion by action within the central nervous system, but demonstrate that the central inhibitory effect of THC does not prevent the release of LH-releasing hormone (LHRH) when the LHRH neurosecretory units are activated by brain stimulation. Thus, the antiovulatory effect of THC appears to result from an inhibition of LH secretion which does not involve the direct blockade of LHRH release.

Animals↗

PubMed1985

Selective release of follicle-stimulating hormone and luteinizing hormone by 5 alpha-dihydroprogesterone and 3 alpha, 5 alpha-tetrahydroprogesterone in pregnant mare's serum gonadotropin-primed immature rats exposed to constant light.

The effects of 5 alpha-dihydroprogesterone (5 alpha-DHP) and 3 alpha, 5 alpha-tetrahydroprogesterone (3 alpha, 5 alpha-THP) on follicle-stimulating hormone (FSH) and luteinizing hormone (LH) release were examined in the pregnant mare's serum gonadotropin (PMSG)-primed immature female rat (8 IU PMSG at 28 days of age) maintained in constant light. Control rats kept in 14L:10D conditions exhibited proestrous-like surges of LH and FSH release with peak levels attained at 1800 h on the second day after PMSG treatment. In rats exposed to constant light, the PMSG-induced surges of LH and FSH were not only delayed until 1000 h on the third day after PMSG, resulting in a delay in ovulation, but were also significantly attenuated when compared to the gonadotropin surges that occurred on Day 2 in rats kept under normal light-dark conditions. The administration of 5 alpha-DHP significantly enhanced the release of FSH at 1000 h on Day 3 when compared to constant light-exposed controls, but had no effect on LH. Treatment with 3 alpha, 5 alpha-THP selectively potentiated the release of LH at 1000 h on Day 3 and had an attenuating effect on FSH release on Days 2 and 3. These observations confirm earlier findings in the immature ovariectomized estrogen-primed rat and suggest that 5 alpha-DHP and 3 alpha, 5 alpha-THP may have significant roles in the regulation of FSH and LH secretion.

5-alpha-Dihydroprogesterone↗

PubMed1984

Selective release of follicle-stimulating hormone by 5 alpha-dihydroprogesterone in immature ovariectomized estrogen-primed rats.

The effect of 5 alpha-dihydroprogesterone (5 alpha-DHP) on gonadotropin release was examined in the immature acutely ovariectomized (OVX) rat primed with a low dose of estradiol (E2). Treatment with various doses of 5 alpha-DHP given in combination with E2 increased levels of follicle-stimulating hormone (FSH) but had no effect on serum luteinizing hormone (LH). A single injection of a maximally stimulating dose of 5 alpha-DHP (0.4 mg/kg) stimulated increases in serum FSH at 1200 h and, 6 h later, at 1800 h. Pituitary LH and FSH content was dramatically enhanced by 1600 h and levels remained elevated at 1800 h. The administration of pentobarbital at 1200 h, versus 1400 h or 1600 h, prevented the increase in basal serum FSH levels at 1800 h, implying that the release of hypothalamic LH releasing hormone (LHRH) is modulated by 5 alpha-DHP. In addition, changes in pituitary sensitivity to LHRH as a result of 5 alpha-DHP were measured and a significant increase in the magnitude of FSH release was observed at 1200 h and 1800 h. Although the LH response to LHRH in 5 alpha-DHP-treated rats was not different from controls, the duration of LH release was lengthened. These results suggest that 5 alpha-DHP may stimulate FSH release by a direct action at the pituitary level. Together, these observations support the theory that 5 alpha-DHP mediates the facilitative effect of progesterone on FSH secretion and further suggests an action of 5 alpha-DHP in this phenomenon at both pituitary and hypothalamic sites.

20-alpha-Dihydroprogesterone↗

PubMed1984

Selective release of luteinizing hormone by 3 alpha-hydroxy-5 alpha-pregnan-20-one in immature ovariectomized estrogen-primed rats.

This study investigated the role of 3 alpha-hydroxy-5 alpha-pregnan-20-one (3 alpha,5 alpha-THP) in the modulation of gonadotropin secretion using the immature ovariectomized (OVX) rat primed with a low dose of estradiol. A treatment regimen of either 0.2 or 0.4 mg/kg of 3 alpha,5 alpha-THP given in conjunction with estradiol for 4 days significantly increased levels of serum luteinizing hormone (LH) but had no effect on serum follicle-stimulating hormone (FSH). Estrogen-primed rats receiving a single injection of 3 alpha,5 alpha-THP at 0930 h showed an increase in serum and pituitary LH levels at 1200 h and 1500 h. At 1800 h, only pituitary levels of LH remained significantly higher than controls. An injection of 3 alpha,5 alpha-THP at 1230 h in estrogen-primed rats resulted in enhanced levels of pituitary LH at 1500 h and elevated levels of both serum and pituitary LH at 1800 h. When 3 alpha,5 alpha-THP was given at 0930 h and 1230 h, elevated serum levels of LH were maintained for over 6 h. The administration of pentobarbital (Pb) 30 min after an injection of 3 alpha,5 alpha-THP at 0930 h or 1230 h prevented the increases in serum LH at 1200 h, 1500 h or 1800 h. This suggests that LH-releasing hormone (LHRH) is involved in mediating the LH response by 3 alpha,5 alpha-THP. There was no change in the sensitivity of the pituitary to LHRH following 3 alpha,5 alpha-THP treatment, indicating the absence of a pituitary effect of this steroid.

Animals↗

PubMed1984

Effects of delta-9-tetrahydrocannabinol on reproductive neuroendocrine function in the female: animal studies.

The rat experimental model has been utilized to demonstrate pronounced suppressive effects of THC on the secretion of both LH and PRL, a point of considerable interest since the tonic secretions of these two hormones are regulated in opposite fashions, that of LH requiring active stimulation, and that of PRL, continued inhibition. Moreover, both the tonic and surge modes of secretion of both hormones are inhibited or completely blocked by THC action even though these different secretory modes are presumed to be governed by different CNS regulatory mechanisms. The most direct explanation for this broad inhibitory capability of THC would be direct inhibitory action on the pituitary cells secreting LH and PRL. However, experimental evidence drawn from the rat model, consistent with that from other species, provides no support for the possibility of direct pituitary inhibition of significant consequence. Instead, the evidence strongly favors the hypothesis that THC exerts its neuroendocrine action centrally and thereby influences pituitary function through alterations in the release of hypothalamic hormones into the hypophysial portal circulation. With the evidence favoring a central neuroendocrine mechanism for THC action, the rat model becomes particularly valuable because of the enormous body of information already available regarding neuroendocrine function in that species. Initial experiments with the rat have failed to provide evidence supporting the possibility of direct THC action on the hypothalamic neurosecretory neurons terminating in the median eminence.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗