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Biomedical subjects

J T Pan

Publications and source records attributed to J T Pan.

68 records · Page 4Linked to original sources
PubMed1989

Small dose of domperidone potentiated the effects of TRH and serotonin on prolactin release in ovariectomized, estrogen-treated rats.

A transient antagonism of the dopaminergic action by using a dopamine antagonist, domperidone, plus a dopamine agonist, CB154, has been shown to potentiate the effect of thyrotropin-releasing hormone (TRH) on prolactin (PRL) secretion. In order to test whether the serotonin (5-HT)-induced PRL secretion can also be enhanced in a similar way, we used 5-HT instead of TRH in our first experiment. We found that the dose of domperidone used (10 micrograms/rat) seems to be excessive since it induced a marked and substantial increase in PRL release and the use of CB154 further masked the action of 5-HT. We used a smaller dose of domperidone (1 microgram/rat) without the CB154 and found that it induced a moderate amount of PRL release which lasted for over 1 h. Given TRH (1 microgram/rat) or 5-HT (0.3 mg/rat) 1 h later resulted in a significant increase in plasma PRL which was much higher than that induced by TRH or 5-HT alone. The potentiating effect of domperidone was even more significant for the 5-HT- than the TRH-stimulated PRL secretion. Pretreatment with 5-HT or vasoactive intestinal polypeptide (10 micrograms/rat) were without any effect in potentiating the action of TRH. In conclusion, antagonizing the dopamine action appears to enhance the stimulatory effect of TRH and 5-HT on PRL secretion.

Animals↗
PubMed1989

Fentanyl stimulates prolactin release through mu-opiate receptors, but not the serotonergic system.

Both serotonin (5-HT) and opiates exert a stimulatory effect on PRL secretion. Some evidence suggests that the action of opiates may be elicited through serotonergic neurons. We tested this hypothesis in the present study by evaluating the effect of perturbation of the serotonergic system on PRL secretion induced by fentanyl, a potent morphine-like analgesic. Female Sprague-Dawley rats ovariectomized for 3 weeks and given polyestradiol phosphate (0.1 mg/rat) for 1 week were used in the study. Fentanyl, at a dose of 20 micrograms/rat, induced significant PRL secretion that peaked at 10 min and lasted for more than 30 min. Pretreatment with naloxone (0.5 mg/kg BW, ip) did not block the acute phase of PRL secretion, but significantly lowered the PRL level at 30 min. Fentanyl at a smaller dose (5 micrograms/rat, iv) still induced significant PRL release 10, but not 30, min after injection. This effect was significantly blocked by pretreatment with the same dose of naloxone. On the other hand, whereas animals pretreated with ketanserin or LY53857 (both at a dose of 5 mg/kg BW, ip), two specific 5-HT2 receptor antagonists, had no effect on fentanyl-induced PRL secretion, the same treatment significantly blocked 5-HT-induced PRL secretion. Likewise, pretreatment with p-chlorophenylalanine (250 mg/kg BW, ip), a 5-HT synthesis inhibitor, for 2 days had no effect on the action of fentanyl, while 5-HT-induced PRL secretion was significantly augmented. We conclude that fentanyl acts through mu-opiate receptors to stimulate PRL secretion in a process that does not involve the serotonergic system.

Animals↗
PubMed1988

The serotonin 5-HT2 receptor system, but not the alpha 1-adrenergic receptor system, is involved in the estrogen-induced afternoon prolactin surge in the rat.

Ketanserin (Ket), a new serotonergic (5-HT2) antagonist, has recently been shown to block the estrogen-induced afternoon PRL surge (Endocrinology 120: 2070-2077, 1987). It is not certain, however, whether the effect of Ket was due to its serotonergic or adrenergic receptor antagonistic property. Another 5-HT2 receptor antagonist, LY53857, which possesses no alpha 1-adrenergic receptor affinity, as well as an alpha 1-adrenergic receptor antagonist, prazosin, were used in this study to further clarify the mechanism of 5-HT in the control of PRL secretion. Adult female Sprague-Dawley rats ovariectomized for 2-3 weeks and given a single injection of polyestradiol phosphate were studied 6 days later. Ket, LY53857 and prazosin were examined singly or in combination and animals were injected twice on the sampling day at 1200 and 1300h, respectively. The dosages were as follows: Ket and LY53857, 3 mg/kg BW, ip and 2 mg/kg BW, sc; prazosin, 1 mg/kg BW, ip and 0.7 mg/kg BW, sc. Blood samples were drawn from indwelling intraatrial catheters throughout the afternoon PRL surge.

Animals↗
PubMed1988

Modulatory actions of luteinizing hormone-releasing hormone on electrical activity of preoptic neurons in brain slices.

Single unit activity was recorded from 378 neurons, in two preoptic nuclei rich in luteinizing hormone-releasing hormone neurons, using in vitro brain tissue slices which were prepared form either ovariectomized or ovariectomized plus estradiol-treated rats. To test possible transmitter-like actions, agents were injected into the perfusion medium. Luteinizing hormone-releasing hormone excited 46%, inhibited 7%, and evoked biphasic responses in 2% of the 250 units tested. By comparison, two other peptides, thyrotropin-releasing hormone and cholecystokinin-octapeptide sulfated were exclusively excitatory, acting on 55 and 67% of the neurons, respectively. The response to thyrotropin-releasing hormone, cholecystokinin-octapeptide sulfated, and neurotransmitters were prompt, large, and consistent from trial to trial. In contrast, responses to luteinizing hormone-releasing hormone were usually delayed, small, and variable. Responses to the agents tested were not affected by in vivo estradiol treatment. Possible modulatory actions of luteinizing hormone-releasing hormone were tested by comparing the responses of single neurons to norepinephrine and serotonin before and after an application of luteinizing hormone-releasing hormone. In 39 and 20% of the 119 neurons tested, the norepinephrine responses were potentiated and attenuated, respectively, by luteinizing hormone-releasing hormone. In 46 serotonin-responsive neurons, 28% were potentiated and 22% attenuated. These neuromodulatory actions of luteinizing hormone-releasing hormone were specific in affecting only certain responses of certain neurons, and they were not duplicated on the same neurons by thyrotropin-releasing hormone. It appears that luteinizing hormone-releasing hormone may be a neuromodulator in the preoptic area.

Action Potentials↗
PubMed1988

The pharmacologic induction of prolactin release in the medial preoptic/suprachiasmatic nuclei-lesioned, estrogen-treated ovariectomized rat.

It has been shown that lesions of the medial preoptic/suprachiasmatic nuclei (MPO/SCN) abolish the estrogen-induced afternoon prolactin (PRL) surge. Recent studies using both dopamine antagonist and thyrotropin-releasing hormone (TRH) successfully induced an increase in plasma PRL in various animal models. The same drug approach was used in this study in the MPO/SCN lesioned rat to determine whether these areas participated in the induced PRL release. It is concluded that a significant PRL release can be induced by DA antagonism, or TRH stimulation preceded by DA antagonism in the MPO/SCN lesioned, estrogen-treated ovariectomized rat.

Animals↗
PubMed1987

The influence of raphe lesions, p-chlorophenylalanine, and ketanserin on the estrogen-induced afternoon prolactin surge.

Female Sprague-Dawley rats were ovariectomized and 2 weeks later injected sc with 100 micrograms polyestradiol phosphate, a long-acting estrogen, to induce the afternoon PRL surge. In one series of experiments, the dorsal raphe (DRN), median raphe (MRN), and median raphe-pontine (MRN-RPn) regions were lesioned using a radiofrequency lesion maker set at 56 degrees C for 1 min. Lesions were induced, and atrial catheters were implanted on the day of estrogen injection. Six days later, blood samples were obtained every 2 h from 1100-2100 h to monitor the afternoon PRL surge. The animals were killed, and the hypothalami were quickly frozen on dry ice and stored at -60 degrees C for determination of amine content using HPLC with electrochemical detection. The rest of the brain was fixed and sectioned to verify the location of brain lesions. Complete lesions of the DRN markedly attenuated the PRL surge (P less than 0.001) compared to the effect of sham or incomplete lesions. MRN lesions did not significantly alter the PRL surge; however, MRN lesions that included the RPn significantly (P less than 0.001) attenuated the afternoon PRL surge. Significant decreases in serotonin (5-HT) and 5-hydroxyindoleacetic acid concentrations were observed in the arcuate, ventromedial, suprachiasmatic, and medial preoptic nuclei of the hypothalamus, but not in the median eminence of the lesioned rats. DRN and MRN-RPn lesions decreased the 5-HT concentration in the ARC and MPN compared to sham lesion and DRN incomplete lesion values. Other hypothalamic areas did not show a similar effect of the lesions. The concentrations of norepinephrine, dopamine, or dihydroxyphenylacetic acid were not altered by the lesions. In a second series of experiments one group of animals was injected ip with 10 mg/kg ketanserin, a serotonergic antagonist, at 1200 h on the sampling day. A second group was given 250 mg/kg p-chlorophenylalanine (PCPA) at 1700 h for 2 days before blood sampling was initiated on the third day. Both ketanserin and PCPA completely blocked the PRL surge. In the PCPA-injected animals, the 1100 and 1300 h PRL values were significantly higher (P less than 0.01) than those in vehicle-injected controls. Animals injected with ketanserin at 1200 h had a 1300 h PRL value significantly higher (P less than 0.01) than was observed in vehicle-injected animals.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Electrophysiological test of an amphiphilic beta-structure in LHRH action.

Micropipettes were used to record electrical activity from single neurons in hypothalamic tissue slices, in the hypothalamic arcuate nucleus (ARC), and in the periventricular and suprachiasmatic preoptic nuclei (POA). Responses were measured following in vitro application of luteinizing hormone releasing hormone (LHRH), and two analogues: LHRH models 1 and 3. Model 1 (pyroGlu-His-Trp-Ser-Phe-Thr-Ile-Lys-Ile-ThrNH2) had amino acid substitutions in residues 5-10 designed to form an amphiphilic beta-strand structure. Model 3 (pyroGlu-His-Trp-Ser-Phe-Gly-Ile-Lys-Pro-SerNH2) was also designed to possess amphiphilic characteristics, but also more closely to resemble the native peptide. Electrical recording results showed that LHRH was able both to excite or inhibit different hypothalamic neurons, and that it was more effective in the preoptic area than in the arcuate nucleus. Responses to LHRH model 3 were strongly correlated with responses to LHRH, in their occurrence and their direction, for both of the brain regions studied. Moreover, LHRH models 1 and 3 also retained the neuromodulatory effects of LHRH on cellular responses to norepinephrine and serotonin. Thus, LHRH analogues, designed to possess an amphiphilic beta-structure, preserved some of the properties of LHRH when tested electrophysiologically in the central nervous system.

Amino Acid Sequence↗
PubMed1986

Single-unit activity of hypothalamic arcuate neurons in brain tissue slices. Effects of anterior pituitary hormones, cholecystokinin-octapeptide, and neurotransmitters.

Extracellular single-unit activity was recorded from hypothalamic arcuate nucleus (ARC) in brain tissue slices. Adult female Sprague-Dawley rats, ovariectomized or ovariectomized plus estrogen treated for at least 1 week, were used. Resting activity and responses of ARC neurons to six anterior pituitary hormones, or (as a positive control) cholecystokinin-octapeptide sulfate (CCK-8S), and a battery of four neurotransmitters including norepinephrine, serotonin, dopamine, and glutamate were recorded. A total of 263 neurons were recorded. Estrogen treatment did not cause any significant changes in the firing patterns nor in responses to most agents tested except for CCK-8S. A large percentage of the ARC neurons were either silent (40%) or slow-firing units (43% fired less than twice/s). Only a small percentage of ARC neurons (20-30%) responded to the anterior pituitary hormones, and these responses were small, delayed increases in firing despite the fact that CCK-8S stimulated more than half of the neurons with large responses. Glutamate was also excitatory, but not quite as effective as CCK-8S. Norepinephrine and serotonin were equally effective in eliciting a neuronal response (over 70% of units responded with an excitation or inhibition). Dopamine acted like norepinephrine, but was less potent. Since anterior pituitary hormones only weakly affected ARC neurons, these electrophysiological data give scant support to the notion that short-loop feedback is accompanied by electrical changes. In the ARC, however, CCK-8S may play some functional roles that are influenced by estrogen.

Adrenocorticotropic Hormone↗
PubMed1985

The influence of blinding, olfactory bulbectomy and pinealectomy on plasma and anterior pituitary prolactin levels and on uterine and anterior pituitary weights in normal and neonatally androgenized rats.

Lactating Sprague-Dawley rats had their litters adjusted to 8-10 pups on day 3 of lactation favoring females and some litters were injected with 1.25 mg of testosterone propionate to neonatally androgenize (NA) them. At 22-25 days of age both normal and NA animals were ovariectomized (OVX) and subjected to either sham olfactory bulbectomy (ANOS) + sham pinealectomy (PX), blinding (BLD) + ANOS or BLD + ANOS + pinealectomy (PX). At 13 weeks of age all animals were injected with 0.5 mg of polyestradiol phosphate. At 15 weeks of age the animals were fitted with atrial catheters and at 16 weeks of age blood samples (0.3 ml) were obtained every 3 hours over a 24 hour period. Uterine and anterior pituitary (AP) weights were recorded at sacrifice. Plasma and AP were assayed for prolactin (PRL) by RIA and AP were also assayed for PRL using the Nb2 lymphoma cell PRL bioassay. In both normal and NA animals, BLD + ANOS suppressed plasma PRL levels and PX partially prevented this response. Uterine weights were similar among groups while AP weights were significantly lower for sensory deprived animals. Anterior pituitaries extracted at pH 7.6 had a PRL concentration that was higher for the BLD + ANOS groups when estimated by either RIA or BA, a result that was not observed when the AP were extracted at pH 10.6. The amount of PRL extracted at pH 10.6 was twice that obtained at pH 7.6. Sensory deprived animals that were OVX prepubertally and administered estrogen as adults had a small but significant increase in mean plasma prolactin at 1700 hr. Both normal and NA animals responded in a similar manner to experimental manipulation.

Animals↗
PubMed1985

Central nervous system regions involved in the estrogen-induced afternoon prolactin surge. I. Lesion studies.

Central nervous system regions were examined in long term ovariectomized rats to determine if they are involved in the estrogen-induced afternoon surge in plasma PRL. Adult female rats were ovariectomized 2-3 weeks before bilateral radiofrequency or electrolytic lesions of the brain were placed on day 0. In short term lesion studies, catheterizations and sc injections of polyestradiol phosphate (PEP) were done after the lesion was made; blood sampling was performed on day 2, 3, 4, or 6. In long term lesion studies, the catheterization and PEP injection were done on day 21; blood was collected on day 28. In short term experiments, extensive lesions in the medial preoptic area/suprachiasmatic nuclei (MPO/SCN) completely blocked the PEP-induced afternoon PRL surges sampled on days 2, 3, 4, and 6, while bilateral lesions in the corticomedial amygdala (CMA) had no effect. Discrete bilateral lesions of either MPO or SCN eliminated the afternoon PRL surge on day 6. Discrete, yet complete, lesions of the ventromedial nuclei of the hypothalamus also blocked the PRL surge; however, lesions in the dorsomedial nuclei of the hypothalamus increased, the magnitude of the afternoon PRL surge. In long term studies, lesions of the CMA delayed and attenuated the PEP-induced PRL surge, and lesions of the stria terminalis for 4 weeks had a similar effect. As in the short term lesion studies, long term lesions of the MPO/SCN eliminated the daily rhythm of PRL secretion, although small sporadic rises in plasma PRL levels could be observed throughout the sampling period. It can be concluded that structural integrity of the MPO/SCN and ventromedial hypothalamic nuclei is essential for the estrogen-induced afternoon PRL surge; destruction of the dorsomedial hypothalamic nuclei can increase the magnitude of the afternoon PRL surge; and the CMA is not essential for induction of the PRL surge even though removing its neural input to the hypothalamus for an extended period can delay the onset of and suppress the magnitude of hormone release.

Amygdala↗
PubMed1985

Central nervous system regions involved in the estrogen-induced afternoon prolactin surge. II. Implantation studies.

In the intact cycling female rat, there is a surge of plasma PRL during the afternoon of proestrus. Ovariectomy on diestrous day 1 eliminated the PRL surge completely, and injection of 100 micrograms polyestradiol phosphate, a long-acting estrogen, not only maintained the surge, but amplified and prolonged it. Bilateral implantation of an estradiol (E2)-containing cannula [diluted 1:4 with cholesterol (C)] in the medial preoptic area (MPO), but not in the cerebral cortex (CC), also maintained the surge. In long term ovariectomized rats, bilateral implantation of E2-containing cannulae (1:5, 1:10, 1:20, and 1:200) in the corticomedial amygdala (CMA) or ventromedial nucleus of the hypothalamus or a singular implantation in the third ventricle failed to induce a PRL surge 12 days later. Similar singular implantation in the anterior pituitary (AP) increased the basal levels of plasma PRL compared to those in C-implanted controls, but no surge was evident. Only bilateral implantation of E2 in the MPO induced a small but significant rise of plasma PRL at 1700 and 1900 h. Using higher concentration implants with a higher E2 concentration (1:4) in the MPO and sampling at shorter intervals, significant afternoon PRL surges were induced on days 2-4. However, systemic effects of E2, i.e. vaginal cornification and uterine weight enlargement, were also evident. Similar implants in other brain regions had the same results. Further increasing the E2 to C dilution from 1:10 to 1:200 eliminated the systemic effect of E2 implants, while the PRL surge-inducing ability persisted. It appears that the highest diluted E2 implants (1:150 and 1:200) gave the highest PRL response and persisted for the greatest number of days. Using the highly diluted E2 implants (1:100 and 1:200) in various brain regions, the MPO and the ventromedial hypothalamus were the most sensitive areas in inducing the PRL surge; the other areas studied, including suprachiasmatic nuclei, CMA, AP, and CC were ineffective. In conclusion, highly diluted E2 implants in the brain appear to be effective in obtaining a specific effect on the afternoon PRL surge; the CMA, suprachiasmatic nuclei, AP, and CC are not estrogen feedback sites for the induction of PRL release, and the MPO was the most sensitive area of the estrogen action in the brain regions examined for the induction of the afternoon PRL surge.

Amygdala↗
PubMed1984

The influence of blinding, olfactory bulbectomy, and pinealectomy on twenty four-hour plasma prolactin levels in normal and neonatally androgenized female rats.

The influence of blinding (BLD), olfactory bulbectomy (ANOS), and pinealectomy (PX) on 24-h plasma PRL levels was examined in normal and neonatally androgenized (NA) female rats. NA pups were treated at 3 days of age with 1.25 mg testosterone propionate. Surgery was performed on both NA and normal animals at 22-25 days of age. At 10 weeks of age, animals were vaginally smeared, and at 15 weeks, they were ovariectomized, injected with 0.5 mg polyestradiol phosphate, and fitted with atrial catheters for blood sampling. At 16 weeks of age, blood samples were taken over a 24-h period. In normal animals, BLD plus ANOS resulted in half of the animals exhibiting a diestrous vaginal smear, while the other half exhibited at least one vaginal estrus during the 7-day period when vaginal smears were obtained. Ovarian, oviductal, and uterine weights for blinded (BLD) plus olfactory bulbectomized (ANOS) animals exhibiting diestrous smears were significantly less than those of BLD plus ANOS animals exhibiting periodic vaginal estrus. Plasma PRL levels were lower in both animal groups compared with those in sham controls, but BLD plus ANOS animals with small ovaries had significantly lower plasma PRL and BLD plus ANOS animals with large ovaries. PX of BLD plus ANOS animals resulted in endocrine organ weights comparable to those in controls and elevated the plasma PRL levels to those observed in BLD plus ANOS animals with large ovaries. The PRL levels in BLD, ANOS, and pinealectomized animals, however, were still below those in sham control animals. Sensory deprived animals had peak PRL values at various times of day, and regrouping of the data from the peak PRL time for each animal suggested the presence of a free-running plasma PRL rhythm. In NA animals, a decrease was also observed in endocrine organ weights and plasma PRL for BLD plus ANOS animals similar to that observed for normal BLD plus ANOS animals. However, all animals in the NA BLD plus ANOS group responded with a constant diestrous smear, small ovaries, and low plasma PRL values. PX prevented the decrease in endocrine organ weights and plasma PRL observed in BLD plus ANOS animals. As in normal animals, NA animals also exhibited a free-running PRL rhythm when sensory deprived.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMedDate not supplied

Effects of serotonin depletion by p-chlorophenylalanine, p-chloroamphetamine or 5,7-dihydroxytryptamine on central dopaminergic neurons: focus on tuberoinfundibular dopaminergic neurons and serum prolactin.

Three serotonin (5-HT) neurotoxins, p-chlorophenylalanine (PCPA, 125 and 250 mg/kg, i.p.), p-chloroamphetamine (PCA, 10 mg/kg, i.p.) and 5,7-dihydroxytryptamine (5,7-DHT, 200 microg/rat, i.c.v.) were used to examine whether depletion of central 5-HT has an effect on central dopaminergic (DA) neuronal activities or on prolactin (PRL) secretion. Adult ovariectomized Sprague-Dawley rats primed with estrogen (polyestradiol phosphate, 0.1 mg/rat, s.c.) were treated with one of three neurotoxins and then decapitated in the morning after 3-7 days. Blood sample and brain tissues were collected. The acute effect of PCA (from 30 to 180 min) was also determined. The concentrations of 5-HT, DA and their metabolites, 5-hydroxyindoleacetic acid and 3,4-dihydroxyphenylacetic acid, in the median eminence, striatum and nucleus accumbens were determined by HPLC-electrochemical detection. All three toxins significantly depleted central 5-HT stores by 11-20%. Except for PCPA, neither PCA nor 5,7-DHT had any significant effect on basal DA neuronal activities or PRL secretion. PCA also exhibited an acute effect on the release and reuptake of 5-HT and DA. In summary, depletion of central 5-HT stores to a significant extent for 3-7 days did not seem to affect basal DA neuronal activity and PRL secretion.

5,7-Dihydroxytryptamine↗