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Biomedical subjects

D C Meyer

Publications and source records attributed to D C Meyer.

33 records · Page 2Linked to original sources

The role of endogenous serotonin in phasic LH release.

Injection of the serotonin inhibitor, fluoxetine (75 micrograms) into the hypothalamus (IC) of ovariectomized (Ovx.) rats treated with 17beta-Estradiol (E2) and parachlorophenylalanine (PCPA 150 mg/kg) significantly increased the luteinizing hormone (LH) in these rats 24 hours later when PCPA had suppressed the LH surge in a parallel group of sham rats. There was a temporal delay in these changes of LH (and by implication serotonin metabolism), since there was no significant effect on the blocked LH surge within two hours of the injection. Since steroids play a major role in gonadotropin secretion and PCPA has been shown to depress LH release, it is interesting that E2 increased the rate of H-3 serotonin (1 X 10(-7) M) uptake in hypothalamic synaptosomes. This suggests a mechanism to increase the removal of synaptic serotonin and the low concentrations of serotonin used in these experiments suggest that uptake occurred in the high affinity serotonin uptake pump and can be influenced by ovarian steroids. This is in contrast to the saturation uptake of serotonin which was unaffected by steroids.

Animals↗

Developmental patterns of tyrosine hydroxylase activity in discrete central nervous system regions and serum LH and prolactin in the prepubertal rat.

Changes in tyrosine hydroxylase (TH) activity in the whole hypothalamus and discrete nuclear regions of the limbic system were observed to occur from 10 to 40 days of age in the female rat. In the whole hypothalamus, TH activity increased between 10 and 30 days of age then decreased at 40 days of age. In the preoptic (POA) and suprachiasmatic nuclear areas (SCN), TH activity increased to peak values at 20 days then declined to baseline values at 25 days. However, an increase in TH activity of SCN was again noted at 39 days of age. TH activity in the amygdala area (AMYG) increased to peak values at 25 and 30 days with a return to baseline levels at 35 days, while in the median eminence (ME), TH activity increased at 20 days and remained elevated through 39 days of age. These results show that temporally distinct changes in TH activity occur during development in various areas of the brain. These changes may represent maturation of neuronal control systems known to be involved in adult reproductive function. Serum LH levels in the developing rat increased between days 10 and 25 then showed a precipitous drop at day 30 followed by increased values at days 35-39. Serum prolactin levels remained low through day 20, increased at days 25-30 then decreased on day 35 with a peak at day 37, prior to the onset of puberty. The inverse relationship of LH and prolactin at day 30 suggests a transient inhibitory (antigonadotropin) effect of increasing prolactin levels on LH at this time.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Uptake of serotonin and norepinephrine in hypothalamic and limbic brain regions during the estrous cycle and the effect of neurotoxin lesions on estrous cyclicity.

The temporal pattern of hypothalamic and limbic aminergic activity during the estrous cycle has been measured by changes in the serotonergic and noradrenergic neuronal uptake during the regular estrous cycle. Significant changes (p = 0.006, 0.01) in the uptake of 3H 5-HT and 3H NE were recorded in the suprachiasmatic nuclei (SCN) at 1200 hours on proestrus. Significant changes (p = 0.01, 0.018) in the uptake of 3H 5-HT in the preoptic area (POA) were found at 1200 hours on both diestrus and proestrus while median eminence (ME) 5-HT showed a significant increase only during proestrus (p = 0.001). In the amygdala (AMYG) 3H 5-HT uptake was significantly different at 1200 hours on diestrus and proestrus while 3H NE uptake was significant (p = 0.001) at 1200 hours only during proestrus. The plasma proestrous luteinizing hormone surge occurred at 1700 hours. The serotonin neurotoxin, 5,7-dihydroxytryptamine, was stereotaxically injected through a 30 gauge needle in concentrations of 5-10 micrograms/microliters/minute for 1 minute in various nuclear regions. In the SCN 4 or 5 day estrous cyclicity was interrupted by diestrus for average periods of up to 15 days; in the POA for periods of 10 days; in the ME for periods of 13 days; and in the AMYG for periods of up to 6 days. Sham injections of 5% ascorbic acid had no effect on cyclicity and following these periods of acyclicity rats resumed normal cycles. These lesion effects and patterns of uptake suggest a common timing mechanism utilizing serotonergic raphe systems for neuroendocrine control. Lesions with 5,7-DHT in all four brain regions disrupt cyclicity, but the greatest delays occur in the SCN and ME regions which are particularly critical to intrinsic neuroendocrine rhythms. Patterns of increase in reuptake capacity in all 4 regions occur 3 hours prior to the critical period for the plasma LH surge and may be an important mechanism for many types of neuroendocrine events including ovulation.

5,7-Dihydroxytryptamine↗

Hypothalamic and raphe serotonergic systems in ovulation control.

The role of hypothalamic and midbrain serotonergic systems in the control of ovulation in the rat has been investigated using 5,7-dihydroxytryptamine (5,7-DHT) lesioning in conjunction with desmethylimipramine pretreatment. Intracisternal injection of 5,7-DHT (100 or 200 microgram) produced a dose-dependent decrease in the incidence of ovulation induced by PMS gonadotrophin (PMSG; 8 IU sc on day 30). Intraventricular injection of 200 microgram 5.7-DHT via the lateral ventricles completely blocked PMSG-induced ovulation. After injection into either site, nonovulatory animals were in proestrus on day 33 and contained fluid-filled uteri. Intracerebral injection of 5,7-DHT into the dorsal or median raphe significantly decreased the numbers of animals induced to ovulate. The extent and specificity of these chemical lesions were evaluated in the suprachiasmatic (SNR) and arcuate-median eminence regions of PMSG-treated rats using an in vitro uptake model. A general feature of every case of inhibited ovulation was the significant decrease in uptake of serotonin in the SNR, indicating destruction of serotonergic inputs to this region. This suggests that serotonergic SNR input from the dorsal raphe region is essential to ovulation. Median raphe lesions appeared to be more extensive than dorsal raphe lesions, involving serotonergic projections to the arcuate-median eminence region. In addition, ascending noradrenergic projections to the SNR were significantly destroyed, also implicating these systems in ovulation control.

5,7-Dihydroxytryptamine↗

Effects of continuous light and darkness, and of pinealectomy, adrenalectomy and gonadectomy on uptake of 3H-serotonin by the suprachiasmatic nuclear region of male rats.

Rats exposed to continuous light show no significant differences in serotonin (5-HT) uptake by the suprachiasmatic nuclear region (SNR) at 10.00 and 22.00 L, while in continuous darkness, the uptake at 10.00 D is significantly higher than uptake at 22.00 D. In consideration of the role of the suprachiasmatic nucleus in light-mediated control of neuroendocrine activity, this suggests endogenous generation or control of this uptake rhythm. An effect of sham-pinealectomy in decreasing 5-HT uptake was found, but cannot be fully interpreted at this time. The lack of effect of castration or adrenalectomy suggests that these endocrines have little if any direct effect on 5-HT mechanisms in the SNR.

Adrenalectomy↗

Hypothalamic and suprachiasmatic uptake of serotonin in vitro: twenty-four-hour changes in male and proestrous female rats.

Twenty-four-hour changes in the in vitro serotonin (5-HT) uptake capacity of hypothalamic homogenates and of "Vibratome" slices of the suprachiasmatic nuclear region (SNR) of the hypothalamus were studied in 60-90-day-old Holtzman (albino) rats. Animals acclimated to artificially illuminated (fluorescent, LD 12:12) and temperature controlled (22 +/- 2 C) rooms were killed 6% each of 8 time points. Synaptosomal fractions from homogenates of whole hypothalamus, and slices of the SNR were incubated for 20 min in Krebs-Henseleit buffer with [3H]5-HT. Males showed a single daily peak in SNR uptake at the start of darkness, and a minimum near the onset of light, while a more complex pattern containing 3 peaks and minima occurred in uptake by hypothalamic homogenates. Proestrous females showed a single high amplitude peak SNR uptake during the critical period, just prior to the plasma LH peak determined in the same animals by radioimmunoassay. It is suggested that this short-term and 4-fold increase in SNR uptake of 5-HT may serve to limit free 5-HT and its inhibitory or other effects on the gonadotropin release hormone system and thereby on LH release and ovulation.

Animals↗

The effects of perinatal exposure to nicotine on plasma LH levels in prepubertal rats.

Adult female rats were chronically treated with nicotine administered via the drinking water during pregnancy and/or lactation. The approximate doses of nicotine consumed per day were 2.4 mg/kg and 4.5 mg/kg of body weight. The pups were weaned at 20 days of age. The pups were killed by decapitation on postnatal days 20, 30, or 40 and plasma from heparinized trunk blood was assayed for luteinizing hormone (LH). At 30 days of age untreated male and female offspring had the highest levels of plasma LH compared to 20 and 40 days of age. This level was not affected by any subsequent dose or treatment. Prepubertal females exposed to nicotine during pregnancy failed to exhibit the pattern of LH levels seen in control animals, whereas those exposed during lactation or throughout the perinatal period showed a distinctive pattern of plasma LH. Chronic exposure of female offspring to the low dose of nicotine during lactation tended to increase plasma LH levels at 20 and 40 days. Female offspring exposed to nicotine during pregnancy or to the low dose during lactation showed significant deficits in body weight at 40 days of age which appeared to correlate with a delay in vaginal opening. The results suggest that perinatal exposure to maternally administered nicotine may disrupt normal patterns of LH release in the offspring of both sexes and alter sexual development in female offspring.

Administration, Oral↗

Serotonin and norepinephrine uptake in discrete brain regions during the pregnant mare serum (PMS) induced estrous cycle in the rat.

The role of hypothalamic and limbic aminergic systems in neuroendocrine control in the rat has been investigated by measuring the temporal changes in serotonergic and noradrenergic neuronal uptake in a model of the estrous cycle. Using the pregnant mare serum (PMS) model of induced ovulation and an in vitro uptake system, serotonergic activity reached peak values (p = 0.01) in the suprachiasmatic nuclear region (SNR) and median eminence (ME) (p = 0.007) during the critical period for luteinizing hormone release. 5, 7-dihydroxytryptamine lesions of the SNR or ME regions inhibited PMS induced ovulation suggesting that at least in these two areas a certain amplitude of 5-HT activity may be required at some time prior to the critical period for LH release. Serotonergic uptake during diestrus in the median eminence showed maximum values during the mid-light phase suggesting a role for this region in ovulation control mechanisms prior to the proestrous critical period. Significant changes (p = 0.001) in serotonergic uptake were found in mid to later light diestrus in the amygdala. This pattern was repeated during proestrus and estrus only in the amygdala suggesting a daily pattern of serotonergic uptake during the estrous cycle. Significant changes (p = 0.001) in noradrenergic uptake only occurred in the amygdala during proestrus.

Animals↗