Derek Gupta

Ontogeny of Circadian Rhythmicity for Melatonin, Serotonin, and N‐Acetylserotonin in Humans

The serum concentration of melatonin, serotonin, and N‐acetylserotonin were measured by RIA procedures in 28 infants aged 1 week to 9 months. Blood specimens were obtained at 1200 hr and 2400 hr. A day‐night difference in serum serotonin was present immediately after birth. A significant (P < 0.001) decrease in serum serotonin concentrations at 1200 hr and 2400 hr was observed from the first month of age to the third to ninth month of age. A significant (P < 0.05) difference in day‐night N‐acteylserotonin concentration is first seen at age 1–3 months. Serum melatonin concentrations, though detectable, did not show any day‐night difference at birth. Melatonin concentrations progressively increased up to the third month of age, and a significant (P < 0.01) day‐night difference appeared thereafter. The results indicate that in humans the circadian organizatijon for serotonin already exists at birth, and the circadian melatonin rhythm develops after birth.

Evidence for Modulation of Melatonin Secretion in Men With Benign and Malignant Tumors of the Prostate: Relationship With the Pituitary Hormones

The serum levels of the pineal hormone melatonin were determined by radioimmunoassay (RIA) in 4‐h intervals throughout a 24‐h period in elderly men with different types of prostate tumors: benign prostatic hyperplasia (BPH, n = 13), incidental carcinoma (PCi, n = 5), and nonmetastasizing carcinoma (PC, n = 9), as well as in young men (YM, n = 10). Simultaneously, the pituitary hormones prolactin, growth hormone, luteinizing hormone and follicle‐stimulating hormone were measured by RIA. All subjects were untreated and free of serious complaints, and they stayed in the same environment. The data were analyzed by the population mean‐cosinor method, and linear correlation coefficients between the five hormones were calculated for each group.

Effect of the pineal gland on circadian rhythmicity of colony forming units for granulocytes and macrophages (CFU-GM) from rat bone marrow cell cultures

Abstract: The present study provides evidence that the pineal gland has a physiological role in the proliferation of colony forming units for granulocytes and macrophages (CFU‐GM). A biphasic circadian rhythm of CFU‐GM proliferation in rat bone marrow cell cultures (BMC) from intact animals peaking at 0600 and 1800 was observed. Pinealectomy (Px) at 1600 obliterated the circadian rhythm patterns of CFU‐GM. Afternoon injections of melatonin (1630, 20 (μg/per day for 10 days) to Px animals restored the rhythmicity. When pinealectomy was done at 0800, the morning peak remained unaltered and the colony number at 1800 was higher than that found in the afternoon Px animals. In conclusion, the pineal gland or its main hormone melatonin seems to have a regulatory role in the proliferation of CFU‐GM in rat BMC. Further, the expression of the activity of CFU‐GM in rat BMC depends on the time when pinealectomy is done or melatonin is substituted.

Functional brain organization, handedness, and immune vulnerability in musicians and non-musicians

In the current investigation an approach has been made to explore possible relations between musical talent, left-handedness, anomalous dominance for verbal materials, and immune vulnerability. Fifty-one young adult musicians and non-musicians were tested with Wings Standardized Tests of Musical Intelligence, with a handedness questionnaire, a dichotic listening task, and with a questionnaire assessing asthma/allergies, migraine and myopia. In addition, IgE, Ig total, beta-endorphin, testosterone, and estradiol were measured in blood serum. Musical talent was related to left-handedness and to anomalous dominance; immune vulnerability was found in female musicians, and in subjects with reversed dominance for language functions as well as in male left-handers, independently of musical talent.

Plasma Adrenocorticotropin, Cortisol, and Dehydroepiandrosterone Response to Corticotropin-Releasing Factor in Normal Children during Pubertal Development

ABSTRACT: The adrenocorticotropin (ACTH), Cortisol, and dehydroepiandrosterone responses to synthetic human corticotropin-releasing factor (CRF) were studied in 28 endocrinologically healthy children (age 1–16 yr) and in six adult volunteers (age 24–42 yr). CRF was given as an intravenous bolus (1 μg/kg body weight) between 0900 and 1000 hr. Significant increments in ACTH and Cortisol levels after CRF were observed in all subjects, with an ACTH peak value of 48.2 ± 3.4 pg/ml at 10 min (p < 0.001). The ACTH and Cortisol response patterns after CRF did not change with age or pubertal maturation and did not differ in children and in adults. In contrast, the dehydroepiandrosterone response to CRF clearly was related to the stage of pubertal development. The peak value after CRF significantly increased from puberty stage 1 to puberty stage 5 (164 ± 18 versus 779 ± 86 ng/100 ml, p < 0.001). In adults, the mean dehydroepiandrosterone peak value after CRF did not differ from that of P5 children. These results show that CRF can be given safely to children. The absence of age-dependent ACTH and Cortisol responses and a dehydroepiandrosterone response changing with pubertal maturation points to the existence of factors involved in the control of adrenal androgen production other than ACTH.

Ontogeny, Circadian Rhythm Pattern, and Hormonal Modulation of 5α-Dihydrotestosterone Receptors in the Rat Pineal

Some physiological parameters of pineal 5 alpha-dihydrotestosterone receptor in the rat such as ontogeny, circadian rhythm pattern, and its modulation by various neuropeptides and neurotransmitters which have profound influences on the pineal hormone melatonin were examined. Pineal 5 alpha-dihydrotestosterone receptors measured at different ages of the animal revealed that on day 10 both cytosolic receptor (CR) and nuclear receptor (NR) levels were high. With growth and development both groups of receptors declined and during puberty started again to rise. During adulthood both receptors were high; however, NR rose further with full maturation. Both groups of receptors showed circadian rhythmicity. While the CR was significantly higher at 6.00 h than at any time point through 24 h, the NR peaked at 18.00 h when the difference between both groups was maximum. Castration caused significant increment of NR. Treatment of castrated animals with a low dose of testosterone propionate (0.25 mg) significantly stimulated both receptor groups, while treatment with a high dose (2.5 mg) failed to do so. Treatment with various substances such as antiandrogen, opioids, neuropeptides, and neurotransmitters significantly modulated the pineal androgen receptor population: cyproterone acetate and monosodium glutamate suppressed CR; growth hormone releasing hormone increased NR; growth hormone release inhibiting hormone had no significant effects on either group of receptors; exogenous melatonin and norepinephrine increased NR; beta-endorphin increased only NR, but methionine enkephalin stimulated both, and epithalamine had no significant effects on either group of receptors, but thymosin alpha 1 increased NR.(ABSTRACT TRUNCATED AT 250 WORDS)

Elevated prolactin levels in human aqueous humor of patients with anterior uveitis

Evidence is accumulating that prolactin (PRL) may play a physiological role in the regulation of humoral and cell-mediated immune responses. On the basis of these observations, we measured levels in the serum and aqueous humor of 28 patients with cataract or anterior uveitis with concomitant cataract. Intraocular concentrations were measured in a range from 0.1 to 3.4 ng/ml. whereas serum PRL levels failed to show significant differences between the two groups (P=0.39), intraocular concentrations were significantly higher in uveitis patients (P<0.001). The level in aqueous humor did not reflect the serum concentration in either group. To the best of our knowledge, this is the first study measuring PRL concentrations in human aqueous humor.

Tumor-Inhibiting Activity in the Rat Pineal Gland Displays a Circannual Rhythm

The aim of this study was to investigate whether the tumor‐inhibiting activity present in the rat pineal gland undergoes seasonal fluctuations as do other pineal substances. Crude ethanol extracts of rat pineal glands were tested for tumor‐inhibiting activity in an in vitro microbioassay using human erythroleukemia cells which could not be inhibited by melatonin. Highest activity was detected in summer and least inhibition and even stimulation were observed in winter. There were no differences in activity between animals of different age, sex, or strain. Therefore, season seems to be the factor that exerts the most important influence on the content of tumor‐inhibiting activity in the rat pineal gland. Correlation with seasonality in the occurrence of cancer is discussed.

Sex steroid hormones during multiphase pubertal developments

Abstract Somatic changes during adolescence were related in this study to the breast or genitalia maturational ratings described by Tanner [1]. Urinary androsterone excretion in boys as well as in girls paralleled more the development of skeletal age as a maturational parameter than the chronological age of the adolescent individuals. Sex differences became obvious in relating the androsterone excretion in boys or girls to the skeletal maturity. A similar relationship between girls and boys to the skeletal development was encountered measuring testosterone excretion values. Plasma estradiol and estrone concentrations in girls and plasma testosterone and dihydrotestosterone levels in boys exhibited close correlations to the pubertal developmental stages. Estradiol levels in boys were highly correlated to testosterone concentrations, indicating that perhaps a significant portion of the estrogen is derived from circulating androgens. 5α-androstane-3α, 17β-diol showed a rise during the maturational stages in boys. Changes in the relationship between dihydrotestosterone/testosterone and androstanediol/testosterone indicate that there is an increment of 5α-reductase activity at the beginning of puberty. Longitudinal studies revealed parallelism between testosterone excretion in the urine and the plasma testosterone concentrations, showing the most marked increments between ages 12 and 14 years. In the rat it was found that plasma testosterone levels rose dramatically after the 25th day of life, the surge in dihydrotestosterone occurred at the 26th day of life, but the peak is reached later. These changes were compared to LH and FSH levels. The rate of increment in plasma FSH concentrations is greatest between 16 and 20 days of age and followed by a spurt in the LH concentration after day 20 of age. The abrupt rise in plasma testosterone seen after day 26 is perhaps mediated by the sudden rise in the two gonadotropins. Changes due to castration and cryptorchidism are discussed.

Rhythm development in pineal and circulating serotonin, N-acetylserotonin, and melatonin in Syrian hamsters.

The ontogeny of diurnal rhythm patterns in the pineal and serum levels of melatonin, serotonin, and N‐acetylserotonin was studied in Syrian hamsters (Mesocricetus auratus) from birth to adulthood. The pineal and blood specimens were collected at 1100 h and 0200 h, and the compounds were measured by radioimmunoassay (RIA) procedures. Pineal melatonin and serotonin did not show any circadian rhythm at day 5 of postnatal age. At this age N‐acetylserotonin was undetectable in the light phase but became manifest at night. By 10 days of age pineal serotonin registered an established rhythm pattern, with a higher level during the day. The occurrence of circadian rhythm in pineal melatonin was delayed and manifested first at 25 days of age. At this age, the first detectable daytime level of N‐acetylserotonin also occurred. Circadian rhythm in serum melatonin was also established at this age. The serum serotonin did not evince any rhythm pattern throughout the observation period, except at day 17 of postnatal age. The massive concentration of daytime serotonin in the pineal was not reflected in the circulatory system. For serum N‐acetylserotonin there was no discernable day‐night rhythm in all age groups, except at 25 days of age. The results show that the timing of the appearance of various compounds in the neonatal pineal is variable; the release of the substances does not always reflect their synthesis; the ontogenesis of circadian rhythm is a part of the maturational process; and 25 days of age is a rather critical time in development.