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Biomedical subjects

D C Klein

Publications and source records attributed to D C Klein.

At least 181 records · Page 10Linked to original sources
PubMed1980

Melatonin inhibition of the in vivo pituitary response to luteinizing hormone-releasing hormone in the neonatal rat.

The effects of melatonin on the in vivo pituitary LH response to LH-releasing hormone (LHRH) were examined in neonatal male and female rats, in 35- to 44-day-old male rats, and in 35- to 44-day-old male animals which had been either pinealectomized or maintained in constant light for at least 3 weeks before use. Animals were given saline or melatonin (1--100 micrograms/rat) followed within 30 sec by saline or LHRH (10--1,000 ng/rat) at separate subcutaneous sites. Blood was collected following decapitation either without prior injection or 15, 30, 45, or 60 min afterwards. Serum LH concentrations were determined by double antibody radioimmunoassay. In neonatal male and female rats, melatonin (1 microgram) significantly (p less than 0.01) suppressed by approximately 65% serum LH at 15 min after LHRH. Suppression was maintained for at least 60 min, a finding which indicates that melatonin blocks rather than delays the response to LHRH. By contrast, in normal, pinealectomized, and constant light older male rats, melatonin (100 micrograms) had no detectable effect on either the magnitude or the time course of LH release by LHRH. These data extend our previous in vitro findings by demonstrating that melatonin is a potent inhibitor of the in vivo pituitary response to LHRH in neonatal rats but not in older animals. Neither pinealectomy nor constant light, both of which are assumed to reduce pineal melatonin production, for at least 3 weeks before use restores neonatal pituitary responsiveness to the pineal indole in the older animals.

Aging↗
PubMed1980

Effects of 6-hydroxy-, 6-fluoro-, and 4,6-difluoromelatonin on the in vitro pituitary response to luteinizing hormone-releasing hormone.

The effects of 6-hydroxy-, 6-fluoro-, and 4,6-difluoromelatonin on the pituitary LH response to LHRH were studied in organ culture. Anterior pituitary glands obtained from 5-day-old female rats and maintained in culture in control medium for 24 h were incubated for an additional 6 h with the test substances. Medium LH content was determined by double antibody RIA. 6-Hydroxymelatonin, the primary metabolite of melatonin after iv administration, had no detectable effect on either basal or LHRH-stimulated release of LH when tested at concentrations up to 10(-6) M. This finding demonstrates that hydroxylation in position 6 will inactivate melatonin with regard to its pituitary effect. By contrast, 6-fluoro- and 4,6-difluoromelatonin at nanomolar concentrations both markedly suppressed the LH response to LHRH. Fluorine substitution for hydrogen in position 6, therefore, does not detectably interfere with activation of the pituitary melatonin receptor. Furthermore, in view of the increased strength of the carbon-fluorine bond compared to the carbon-hydrogen bond, the 6-fluoro analogs should be less susceptible than melatonin to inactivation by hydroxylation in position 6. These analogs, therefore, may be useful as long acting inhibitors of reproductive function in the intact animal.

Animals↗
PubMed1980

Ontogeny of the pineal melatonin rhythm in the Syrian (Mesocricetus auratus) and Siberian (Phodopus sungorus) hamsters and in the rat.

The ontogeny of the pineal melatonin rhythm was determined in three rodent species. Pineal glands were obtained either during the day or during the expected peak in melatonin at night. In all species the rhythm was first detected during the second week of life. Investigations of the photic regulation of pineal melatonin revealed that light could inhibit the nocturnal increase in melatonin in all species by the end of the second week of life. These studies indicate that for these species the development of the rhythm in pineal melatonin and the development of the mechanism involved in the photic suppression of the nocturnal increase in melatonin are independent of the role the pineal gland plays in regulating reproductive function in response to changes in environmental lighting.

Aging↗
PubMed1980

Studies on the daily pattern of pineal melatonin in the Syrian hamster.

In the Syrian hamster, a sharp peak in pineal melatonin occurs toward the end of the dark period. In the present communication, we describe characteristics of this rhythm. First, the time of the initial increase in pineal melatonin is not altered by daily melatonin injections that induce gonadal regression. Second, the rapid decrease of pineal melatonin in the morning is not prevented by acutely extending the dark period. Third, a consistent nocturnal increase in pineal melatonin is not observed in a 20-h light, 4-h darkness lighting schedule. However, acute exposure to a longer dark period, at the appropriate time of day, allows expression of the pineal melatonin rhythm in these animals. Finally, the rhythm in pineal melatonin appears to be truly circadian and is tightly coupled to the circadian rhythm in running activity.

Animals↗
PubMed1979

Pineal N-acetyltransferase and hydroxyindole-O-methyltransferase: control by the retinohypothalamic tract and the suprachiasmatic nucleus.

The visual pathway and central neural structures involved in the photic and endogenous regulation of the activity of pineal N-acetyltransferase and hydroxyindole-O-methyltransferase were investigated. The results indicate that the visual pathway regulating both enzymes is the retinohypothalamic tract, and that the inferior accessory optic tract is clearly not involved in the regulation of hydroxyindole-O-methyltransferase activity, as has been previously thought. In addition, the suprachiasmatic nucleus was found to be necessary for the generation of a rhythm in N-acetyltransferase activity in blinded animals, and to be responsible for the tonic elevation of hydroxyindole-O-methyltransferase activity in blinded animals. Finally, it was concluded that the rapid and large daily changes in N-acetyltransferase activity seen in a normal lighting cycle and the much slower and smaller changes in hydroxyindole-O-methyltransferase activity seen only after weeks in constant lighting conditions are mediated by the same neural tract; the different time courses of the effects of environmental lighting may be explained on the basis of different intracellular regulatory mechanisms.

Acetylserotonin O-Methyltransferase↗
PubMed1979

Taurine: stimulation of pineal N-acetyltransferase activity and melatonin production via a beta-adrenergic mechanism.

Pineal glands convert [3H]tryptophan to [3H]N-acetylserotonin and [3H]melatonin in organ culture. Taurine treatment increases the rate of production of these compounds 40- and 25-fold respectively by stimulating the activity of N-acetyltransferase. This stimulation is blocked stereospecifically by L-propranolol, indicating that taurine is probably acting via beta-adrenergic receptors. Taurine is active in stimulating N-acetyltransferase activity in denervated glands, suggesting that it might interact directly with the beta-adrenergic receptor, and not by causing the release of norepinephrine from nerve terminals.

Acetylserotonin O-Methyltransferase↗
PubMed1979

Maternal-fetal transfer of melatonin in the non-human primate.

Melatonin was detected in the circulation of the near-term rhesus monkey (Macaca mulatta) and baboon (Papio papio) fetus. We determined whether the source could be the mother by studying placental transfer of melatonin in the rhesus monkey. When [3H]melatonin was administered i.v. to the mother it promptly appeared in the fetal circulation; the rates of disappearance of [3H]melatonin in the maternal and fetal circulations were parallel. The rapid decrease in circulating [3H]melatonin was associated with a rapid accumulation of [3H]melatonin-metabolites in the maternal and fetal circulations. Although the pattern of appearance of metabolites was similar in both circulations, relatively less [3H]melatonin-metabolites appeared in the fetal circulation. Acute changes in total maternal plasma melatonin, experimentally produced by giving a 20 min infusion of melatonin, were rapidly reflected in the fetus. This suggests that a daily rhythm in maternal melatonin would generate a similar rhythm in the fetus. The fetal monkey pineal was found to have the two enzymes necessary for the conversion of serotonin to melatonin. It is, however, not known whether fetal melatonin synthesis is rhythmic or the extent to which it could contribute to circulating melatonin levels at this or earlier stages of gestation.

Acetylserotonin O-Methyltransferase↗
PubMed1979

A diurnal melatonin rhythm in primate cerebrospinal fluid.

Melatonin was measured in cerebrospinal fluid (CSF) withdrawn continuously from partially restrained rhesys monkeys. There was a daily rhythm in CSF melatonin with peak night values 2- to greater than 15-fold higher than day values. The increase occurred shortly after lights were turned off, and the decrease occurred soon after lights were turned on. There was substantial variation in the magnitude of the rhythm among animals. However, there was little day to day variation in the rhythm of individual animals studied for 3 or 6 consecutive days. Although the concentration of melatonin in CSF was lower than that in plasma, the changes in CSF melatonin concentrations seemed to reflect large daily changes in plasma melatonin concentrations.

Animals↗
PubMed1978

Pineal serotonin N-acetyltransferase activity: abrupt decrease in adenosine 3',5'-monophosphate may be signal for "turnoff".

Dispersed pinealocytes have been used to study the role of adenosine 3',5'-monophosphate (cyclic AMP) in the "turnoff" of N-acetyltransferace activity. Activity was first stimulated 100-fold by treating cells with 1-norepinephrine. 1-Propranolol acted stereospecifically to rapidly reverse this, resulting in a 70 percent loss of enzyme activity within 15 minutes. An even more rapid 1-propranolol-induced decreased in cyclic AMP also occurred. This together with the observation that the inhibitory effect of 1-propranolol on N-acetyltransferase was blocked by dibutyryl cyclic AMP and phosphodiesterase inhibitors indicate that an abrupt decrease in cyclic AMP may be the signal for the rapid decrease in pineal N-acetyltransferase activity.

Acetyltransferases↗
PubMed1978

Some reflections on community control: a commentary on Nassi.

Community control of social agencies already exists. The question is who from the community is to be in control. Human services agency managers are in the middle between those now in control who sponsor and fund their agencies, on the one hand, and those who are the recipients of their services, on the other. The consumer control movement proposes a radical shift in the equilibrium of power--from community patron-sponsors to community consumer-recipients. Few agency directors identify with disadvantaged groups. Moreover, their agencies typically are part of a service delivery pattern that maintains social inequities, including institutional racism, which pervade the entire society. Therefore, only a few agency heads can be expected to embrace consumer control and to view it as a step towards a more socially just distribution of the human services for which they are responsible.

Community Participation↗
PubMed1978

Transport of maternal[3H]melatonin to suckling rats and the fate of [3H]melatonin in the neonatal rat.

The question of whether maternal melatonin could be transported in milk to suckling rats was investigated because melatonin is probably not produced in these animals during the first 10 days of life. [3H]Melatonin was found to be rapidly transferred from the maternal circulation into lactating mammary tissue, and the stomach of each suckling rat was found to contain [3H]melatonin. To study the fate and tissue distribution of [3H]melatonin originating in the neonatal stomach, suckling rats were given [3H]melatonin by stomach tube; [3H]melatonin was recovered from plasma and seven tissues, including brain, 15 and 60 min later. The general tissue distribution of [3H]melatonin was similar to that found in adult rats. The major [3H]melatonin metabolites in the urine of suckling rats, as the adult rats, were the conjugates of 6-hydroxy-melatonin.

Animal Population Groups↗