Biomedical subjects

R W Rivest

Publications and source records attributed to R W Rivest.

At least 19 recordsLinked to original sources

PubMed1991

Sexual maturation in female rats: hereditary, developmental and environmental aspects.

Two physiological components of sexual maturation, vaginal opening and first estrus, apparently evolve similarly in Wistar and Sprague-Dawley rats. However, a bimodal distribution in the frequency of the days of vaginal opening is observed within a given strain, which is less related to heredity than to the timing and type of experiment. In addition, when the modulators of sexual maturation are reviewed, it can be observed that sensitivity to external stimuli can vary even within a strain. For a defined set of breeding conditions, one group of rats can be more susceptible to changes in the lighting regimen and not be affected by controlled stressors, while another group responds more to stress and less to light. The reason for susceptibility to one rather than another environmental factor under similar breeding conditions is not understood. In that context, it is difficult to evaluate the role of heredity when we cannot understand the full impact of the environment, not to mention maternal influence in fetal and early life. Using two lines of psychogenetically selected rats, it was possible to show that they had differences in sexual maturation, which strongly suggested a genetic predisposition. Nevertheless, the question arises as to whether the genetic locus directly affects organs implicated in sexual maturation or whether it acts on some unknown factor which only secondarily modifies sexual maturation. In summary, there is more need to understand the role of the environment, including that of the mother early in fetal and neonatal life. It is suggested that the mechanisms underlying organ growth are set for a given species, while developmental and environmental factors fix the timing of vaginal opening and first ovulation. In the rat, there appear to be two times which are preferred for vaginal opening, given the laboratory conditions that have been used in the last 20 or so years: an early period, at 31-35 days, and a late period, at 36-40 days. An explanation for this dichotomy would be that a combination of parameters (not necessarily always the same) is needed for vaginal opening. These parameters oscillate during sexual maturation with different frequencies, which can achieve resonance to lead to vaginal opening and ovulation only during given periods.

Aging↗

PubMed1991

Cardiovascular and endocrine effects of clonidine premedication in neurosurgical patients.

The present study was conducted to examine the haemodynamic and endocrine effects of clonidine, given as sole preanaesthetic medication, in neurosurgical patients. Nineteen patients of ASA physical status I and II, subjected to craniotomy, randomly received po premedication of either clonidine (300 micrograms, n = 9) or placebo (n = 10). Blood pressure and heart rate were monitored continuously, while arterial blood samples were collected at specific times, from induction of anaesthesia to recovery, for the measurement of plasma concentrations of epinephrine, norepinephrine, cortisol, aldosterone, and glucose. Clonidine treatment led to a decrease in mean arterial blood pressure (MABP), heart rate (HR), and plasma cortisol and aldosterone concentrations throughout the study, compared with placebo (P less than 0.05). Clonidine, however, did not prevent increases in MABP (16 +/- 5 mmHg, mean +/- SE, P less than 0.05) and HR (18 +/- 4 bpm, P less than 0.05) during induction of anaesthesia, which was comparable to the placebo group. Plasma catecholamine concentrations did not differ between the two groups. Plasma glucose concentrations increased in both groups at the end of the study (P less than 0.05), but were lower in clonidine-treated patients (P less than 0.05). Though statistically significant, the observed inhibitory haemodynamic and endocrine effects of clonidine seem to be of minor clinical importance. As the action of clonidine on cerebral blood flow regulation is not well known, we see no advantage in the preanaesthetic administration of clonidine to neurosurgical patients with normal cardiovascular status.

Administration, Oral↗

PubMed1990

Effect of different calcium channel blockers on angiotensin II- and vasopressin-induced prostacyclin biosynthesis in vascular smooth muscle cells.

To gain insight with regard to the mode of action of calcium antagonists on the vasculature, we examined the effects of nifedipine, isradipine, felodipine, verapamil, gallopamil, and amlodipine on vasoconstrictor-induced prostacyclin synthesis in vitro. Cultured rat aortic smooth muscle cells were seeded after two to four passages in multiwell plates. After washing of the culture medium and a preincubation period, the cells were exposed for 1 h to either angiotensin II (Ang II) or arginine-vasopressin (AVP) at increasing concentrations between 10(-10)-10(-6) M with or without each calcium antagonist tested at 10(-6) M. At the end of the incubation period, the medium was aspirated, centrifuged, and assayed for its content of protein and of 6-keto-PGF1 alpha by radioimmunoassay. Ang II induced a 15-fold increase and AVP induced a fivefold increase of 6-keto-PGF1 alpha at 10(-6) M. None of the various calcium channel blockers tested showed a significant effect on this agonist-stimulated production of 6-keto-PGF1 alpha. Consequently, calcium-channel blockers with different chemical structure, although known to inhibit agonist-induced vasoconstriction, appear to preserve vasoconstrictor-induced production of prostacyclin, a potent vasodilator and an inhibitor of platelet aggregation.

6-Ketoprostaglandin F1 alpha↗

PubMed1989

Effect of low dose dopamine on hemodynamic and renal function in children.

The purpose of the study was to investigate the effect of low doses of dopamine in children. Fourteen cases were studied after open heart surgery. Cardiac output and renal parameters were determined under baseline conditions and under continuous infusion of dopamine 2.5 and 5 micrograms/kg/min. During the control period cardiac index was 2.62 +/- 0.19 L/min/m2, renal plasma flow was decreased at 269 +/- 41 mL/min/1.73 m2, GFR was 86.6 +/- 9.2 mL/min/1.73 m2, and filtration fraction was elevated at 37.1 +/- 1.9%. Plasma concentration of aldosterone correlated with the filtration fraction. At 5 micrograms/kg/min dopamine increased significantly cardiac output, renal plasma flow, and to a lesser extent GFR, thus decreasing the filtration fraction. At 2.5 micrograms/kg/min dopamine, increased renal plasma flow only in patients older than 5 y and had no effect on the other parameters. The increase of cardiac output in response to dopamine was abolished by propranolol pretreatment. By contrast, the hemodynamic renal response to dopamine was not altered by beta-blockade. These results indicate that 5 micrograms/kg/min of dopamine could prevent renal failure after open heart surgery in children by increasing renal blood flow and attenuating renal compensatory mechanisms.

Adolescent↗

PubMed1989

Differences between circadian and ultradian organization of cortisol and melatonin rhythms during activity and rest.

We compared the cortisol and melatonin circadian and ultradian rhythms in normal men using two approaches: 1) the men were exposed successively to two conditions, one normal and a second chosen to alter differently each of the hormones, i.e. complete bedrest for 34 h (supine, fasting, and under dim light), and 2) analyses of the rhythms using a combination of curve smoothing for the description of the 24-h rhythm, and peak detection and spectral analysis for the measurement of periodic phenomena. Blood was sampled every 30 min from 0700-0700 h. A diurnal rhythm was detected for both hormones, with different underlying frequencies. Plasma cortisol had an ultradian rhythm of 8 h. From 0000-0800 h (night) and 0830-1600 h (early day), the pulsatile activity and baseline values of cortisol were high, while from 1630-2400 h (late day), these variables were low. During complete bedrest, pulsatile activity and baseline values were even higher during the night period, and the nocturnal peak of cortisol, usually present between 0300-1000 h, was split in two, with an early peak at 0000-0400 h. There were two specific events during the day associated with synchronous, high amplitude pulses: awakening and eating at noon. No such pulses occurred at suppertime or when the men fasted. Melatonin secretion was organized around a 5.5-h period. In the rest condition, plasma melatonin values were higher during the night. The 24-h rhythms of cortisol and melatonin were temporally related. Plasma melatonin began to rise when plasma cortisol was at its lowest, it peaked when cortisol began to rise, and it began to decrease when cortisol reached its peak, with a 5-h phase delay between plasma cortisol and melatonin rise at night. In summary, melatonin and cortisol rhythms have different ultradian frequencies, suggesting an intrinsic difference in the mechanisms controlling their secretion. In addition, their responses to restricted physical activity in an environment with dim light were completely different; for plasma melatonin, the change was primarily quantitative, with an increase in total production especially at night, while for plasma cortisol, there was more of a qualitative change, with different patterns of pulsatile activity and possible splitting of the nocturnal peak. The differences in the ultradian organization of these two hormones imply that the correlation between their peaks must depend on a third factor, which is likely to be the 24-h organization of the day.

Activity Cycles↗

PubMed1989

Differential activation of the pituitary-adrenocortical axis after stress in the rat: use of two genetically selected lines (Roman low- and high-avoidance rats) as a model.

We have examined the activation of the pituitary-adrenal axis in two lines of rats, the Roman high (RHA)- and low (RLA)-avoidance rats known to be emotionally different. These rats are selected for rapid acquisition of a conditioned avoidance response (RHA) compared with failure to acquire this response (RLA). In this study the endocrine response (ACTH, corticosterone, aldosterone) of RLA and RHA rats to two types of stress was examined: exposure to open-field stress for 10 min (Op) or exposure to ether vapours for 3 min (E). Basal plasma ACTH concentrations were lower in RLA than in RHA rats (RLA: 110.8 +/- 24.5 ng/l; RHA: 252.7 +/- 60.8 ng/l, P less than 0.05) but the absolute values of ACTH reached after both types of stress were comparable between RLA and RHA rats. Plasma corticosterone and aldosterone under resting conditions were not different between RLA and RHA rats. Plasma corticosterone was higher in RLA following openfield stress (P less than 0.05) while no differences between RLA and RHA were observed after ether stress (RHA: basal = 66 +/- 14.nmol/l, Op = 384 +/- 55, E = 606 +/- 75; RLA: basal = 121 +/- 52, Op = 612 +/- 92, E = 698 +/- 89). Stress-induced increases in plasma aldosterone were higher in the RLA line after both types of stress (RHA: basal = 175 +/- 36 pmol/l, Op = 546 +/- 53, E = 563 +/- 47; RLA: basal = 272 +/- 64, Op = 1246 +/- 91, E = 863 +/- 72).

Adrenal Cortex↗

PubMed1988

Spontaneous and chemoattractant-induced oscillations of cytosolic free calcium in single adherent human neutrophils.

Studies with fluorescent Ca2+ indicators in large populations of neutrophils in suspension reveal a stable base line followed by a rapid agonist-induced elevation of cytosolic free calcium, [Ca2+]i, concomitant with other parameters of cellular activation. To study the role of adhesion in cell activation, we monitored [Ca2+]i in single neutrophils adhered to albumin-coated or fibronectin-coated glass coverslips before and after stimulation with the chemotactic peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP). Human neutrophils loaded with 2 microM fura 2/AM were allowed to adhere to coverslips for 15-20 min at 37 degrees C. [Ca2+]i was monitored with a dual excitation microfluorimeter with a time resolution of 200 ms. Statistical analysis was performed using an algorithm allowing to detect significant [Ca2+]i peaks. 54% of the cells showed spontaneous [Ca2+]i oscillations. The amplitude of these [Ca2+]i peaks averaged 77 +/- 10 nM above basal levels (mean value of 110 +/- 20 nM), and their mean duration was 28 +/- 5 s; periods of [Ca2+]i bursts could last up to 15 min. In "silent" cells exhibiting a stable [Ca2+]i base line without spontaneous oscillations, low concentrations of fMLP (10(-10)-10(-9) M) could induce sustained [Ca2+]i oscillations. By contrast, higher agonist concentrations (10(-6) M) induced a single [Ca2+]i transient followed by a stable base line. 47% of the cells showing spontaneous [Ca2+]i oscillations did not respond to fMLP. Spontaneous [Ca2+]i oscillations depended on the continuous presence of extracellular Ca2+. Therefore: (i) spontaneous oscillations of [Ca2+]i occur in neutrophils adherent to various substrata; (ii) these oscillations do not preclude and can be dissociated from the response to fMLP; (iii) neutrophil functions might be controlled by [Ca2+]i oscillations rather than by sustained alterations of [Ca2+]i.

Calcium↗

PubMed1988

Delayed sexual maturation induced by daily melatonin administration eliminates the LH response to naloxone despite normal responsiveness to GnRH in juvenile male rats.

Daily administration of melatonin (MT) markedly delays sexual maturation in the male Wistar rat. In this study, we have evaluated pituitary responsiveness to GnRH and the level of tonic inhibition by endogenous opioids in normal juvenile male rats and in rats with delayed sexual development induced by daily afternoon MT injection (100 micrograms, s.c.) starting at 20 days of life. Plasma LH responses to repetitive intravenous GnRH administration (100 ng/100 g body weight), or to different doses of GnRH administered subcutaneously (5-100 ng/100 g body weight) were normal in MT-treated rats both at 30 and 40 days of life despite significantly lower number of pituitary GnRH receptors and decreased pituitary gonadotropin content. One naloxone (NAL) injection (2.5-5.0 mg/kg, s.c.) produced a significant increase of plasma LH in normal 40- and 55-day-old rats, which was not seen in MT-treated rats of the same age. In contrast, no increase of plasma LH was seen in 30-day-old control rats nor in MT-treated rats at this age. Pretreatment with morphine sulfate (10 mg/kg, s.c.), or with the potent Met-enkephalin analog FK 33-824 (1.0 mg/kg, s.c.) prevented the NAL-induced rise of plasma LH in control rats at day 40 of life. In all instances, plasma PRL levels were decreased after NAL both in untreated and in MT-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1988

Taste-induced changes in plasma insulin and glucose turnover in lean and genetically obese rats.

Cephalic-phase insulin release (CPIR) and the changes in glucose turnover induced by saccharin ingestion were studied in freely moving lean and genetically obese fa/fa rats equipped with chronic catheters for blood sampling. Six-hour-fasted lean and obese rats were trained to drink 1 ml sodium saccharin (0.15%) or 1 ml glucose (70%), and blood samples were taken before and after the stimuli. As early as 1-1.5 min poststimulus, there was a significant increase in CPIR in lean and obese rats. The amplitude of the CPIR induced either by saccharin or by glucose in the obese rats was significantly higher than it was in the lean rats. The effect of saccharin ingestion on the hepatic glucose production (HGP) and the rate of glucose disappearance (Rd) was studied in 6-h-fasted lean and obese rats, under non-steady-state conditions, according to a method previously validated. Saccharin ingestion produced a significant increase in HGP and Rd in lean and obese rats compared with basal values. The saccharin-induced increments in HGP and Rd were higher in the obese than in the lean animals. We conclude that saccharin (through taste) appears to elicit parasympathetic (insulin release) and sympathetic (HGP increase) reflexes in lean and obese rats. These taste-induced changes in plasma insulin and glucose turnover are exaggerated in the obese rats and may participate in obesity and in insulin resistance of the overall syndrome.

Animals↗

PubMed1987

Short-term and long-term effects of melatonin on GnRH-stimulated gonadotropin secretion in pituitaries of sexually maturing rats.

Melatonin administration has been shown to delay sexual maturation in male rats, through an action which involves decreased binding of gonadotropin-releasing hormone (GnRH) in the pituitary and lower pituitary gonadotropin contents. It has been suggested that melatonin must act at a level higher than the pituitary to provoke these effects, but a direct action of melatonin on the pituitary has not been excluded. Using a cell culture system, the gonadotroph responsiveness to GnRH was studied. Pituitaries were obtained either from rats chronically treated with melatonin and showing delayed sexual maturation, or from control rats. In vitro luteinizing hormone and follicle-stimulating hormone response to GnRH was significantly lower when pituitaries were obtained from melatonin-treated rats. However, this diminished response was directly proportional to the amount of gonadotropin contents in cells, so that relative responsiveness, calculated as the amount of gonadotropins released in relation to the gonadotropin content was similar in cells from control and melatonin-treated rats. It is concluded that the effect of melatonin on the pituitary of male rats results from a decrease of gonadotroph growth or gonadotropin synthesis, as a consequence of a change located at the hypothalamic rather than at the pituitary level. This conclusion is further supported by results showing that melatonin added directly in culture medium prior to GnRH does not modify the pituitary responsiveness to GnRH.

Aging↗

PubMed1987

Plasma growth hormone (GH) response to intravenous GH-releasing factor (GRF) in adult rats: evidence for transient pituitary desensitization after GRF stimulation.

The ability of human (h)GRF-(1-29)NH2 to stimulate GH secretion was studied in cannulated adult rats. In order to suppress endogenous GRF secretion and the inhibitory action of hypothalamic somatostatin (SRIF), rats were anesthetized with sodium pentobarbital. Intravenous administration of hGRF-(1-29)NH2 elicited a dose-dependent response of plasma GH, with 250 ng/kg being the smallest effective dose in male rats. In female rats, for each dose tested (250 to 70,000 ng/kg), the GH response represented only about 60% that of male rats. Repeated iv stimulations with hGRF-(1-29)NH2 at short time intervals (45 min) produced transient desensitization of pituitary responsiveness to GRF: a blunted GH response to the second and third stimulations was observed both in male and in female rats and for each dose tested. Similar blunted responses were also obtained with repeated injections of native hGRF-(1-44)NH2. The possibility that these blunted responses could be due to incomplete suppression of hypothalamic SRIF secretion by sodium pentobarbital was excluded by the use of rats that were passively immunized against SRIF; in these rats, it was shown that at least 65% of the inhibition of the GH response after the second GRF stimulation was unrelated to SRIF action. Similar transient desensitization to repeated hGRF-(1-29)NH2 stimulations was also observed in conscious rats that were passively immunized against SRIF. This occurrence of blunted responses was shown to be related to the length of the time interval between GRF stimulations, with longer intervals resulting in less or no desensitization. It appears thus that modulation of pituitary responsiveness to the action of GRF is mediated by at least two independent mechanisms in the rat: in addition to the inhibitory action imposed by hypothalamic SRIF, which induces periods of refractoriness to the action of GRF, it was shown in this study that in the pituitary level each GRF stimulation also induces a transient desensitization of somatotrophs for about 1 h. This period of refractoriness might not be due to excessive stimulation with GRF, since it was also observed with the lowest dose of hGRF-(1-29)NH2 that gave a significant release of GH. Finally, a sex difference was confirmed for the response of anesthetized adult rats to stimulation with hGRF-(1-29)NH2, reflecting a sex steroid-induced modification of pituitary responsiveness to GRF stimulation.

Anesthesia, General↗

PubMed1987

The female rat as a model describing patterns of pulsatile LH secretion during puberty and their control by melatonin.

A characteristic of the advent of final stages of sexual maturation in the rat, the equivalent of puberty in the human, is the development of a specific pattern of pulsatile GnRH secretion, reflected by an equivalent pattern of LH secretion. Many hypotheses have been put forward to explain these last changes, including a change at the hypothalamic level and a modification of the ovary. These models are developed to include melatonin, an indoleamine produced by the pineal gland, which appears to play a role in the establishment of the final pattern of LH secretion, thus affecting both vaginal opening and subsequent estrous cycles. Prior to first ovulation, pulsatile release of LH acquires at least two types of patterns, one with low-amplitude, high-frequency pulses, announcing a pattern observed in the follicular phase of primates, and one with high-amplitude, low-frequency pulses, mimicking what is seen in the luteal phase of primates. From the results presented, it is postulated that chronic melatonin administration increases the number of patterns typical of luteal phases, and reduces those of the follicular type, resulting in a decrease frequency of LH pulses and longer intervals between estrous cycles.

Animals↗

PubMed1986

Nocturnal urinary melatonin excretion and plasma cortisol levels in children and adolescents after a single oral dose of dexamethasone.

In the present study, the possible relationship between melatonin secretion as reflected by nocturnal melatonin excretion (2000 h-0800 h) and the pituitary-adrenocortical axis was investigated. Nocturnal urinary melatonin excretion and plasma cortisol levels were determined in 41 children with weight problems before and after a single oral dose of dexamethasone. A first group of 15 individuals with normal cortisol cycle (12.2 +/- 1.4 at 0800 h and 3.1 +/- 0.5 micrograms/100 ml at 1700 h), and levels below 1.0 microgram/100 ml after dexamethasone, showed a highly significant increase in melatonin excretion during the night following dexamethasone treatment (63.5 +/- 5.5 ng/12 h vs 33.6 +/- 3.0 for the control night, P less than 0.001). This increase was observed from prepuberty to young adulthood (pubertal stages PI-PV). In a second group of 16 subjects with mean cortisol levels similar at 0800 h and 1700 h (10.7 +/- 1.3 and 9.3 +/- 1.5 micrograms/100 ml respectively), but with a normal cortisol suppression after dexamethasone administration, nocturnal melatonin excretion increased from 21.2 +/- 2.1 to 33.4 +/- 3.0 ng/12 h (P less than 0.01). A significant increase was found in prepubertal children (PI) whereas no change was observed at the end of pubertal development (stages PIV-PV). A third group of 10 patients with both low amplitude cortisol cycles (16.2 +/- 2.5 and 10.8 +/- 2.4 micrograms/100 ml) and abnormal cortisol suppression after dexamethasone administration (9.1 +/- 2.4 micrograms/100 ml), showed no increase in melatonin excretion (24.2 +/- 2.7 and 24.9 +/- 3.7 ng/12 h).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1986

Puberty in the rat: modulation by melatonin and light.

Although a role has been found for melatonin in species which have a seasonal reproductive cycle, very little is known on the role of melatonin in species such as the rat where seasonal cycles are a minor component of reproduction. But the rat is a photosensitive species, because it responds to changes in the lighting environment. Females do not become quiescent but they can have irregular estrous cycles, another way of controlling population dynamics. In this species, exogenous melatonin can exert an antigonadotropic action, providing conditions which apply to other species are also respected for the rat: melatonin must be given at the right time of the day, 9 to 12 hours after the onset of light, and at a given period of life, before the onset of puberty. Melatonin probably acts on the pattern of GnRH pulsatile secretion and the subsequent alterations of the hypothalamic-gonadal axis differ according to the sex of the animal. Endogenous melatonin rhythms are modified by the lighting environment, and results obtained with exogenous melatonin suggest that they could be one of the factors controlling timing of sexual maturation.

Animals↗

PubMed1985

The pineal and pubertal development.

The pineal gland, through its major secretory product melatonin, influences seasonal breeding in species such as the hamster and the sheep. Recent studies from our laboratory have shown that melatonin also affects sexual development in the rat. A role for melatonin in humans has not yet been found. The laboratory rat is sensitive to daily administration of melatonin at the beginning of sexual maturation. The male rat is most sensitive between day 20 and day 30 of life. Melatonin does not permanently inhibit sexual maturation, since normal but delayed sexual development occurs after 45 days of life whether melatonin administration is discontinued or maintained indefinitely. In female rats, daily injection of melatonin during the prepubertal period delays the vaginal opening and disrupts the normal cyclicity of the first oestrous cycles. In both male and female rats, the inhibitory action of melatonin is highly dependent upon the time of injection, with maximal effects when melatonin is given in the late photoperiod. The inhibitory action of melatonin is most likely exerted at the hypothalamic level, possibly through interference with the control of pulsatile secretion of gonadotropin-releasing hormone. In contrast to some published work, our experiments provide no evidence for modifications of diurnal or nocturnal melatonin secretion during puberty in humans. Our results with the rat indicate that melatonin may be an important factor for the timing of sexual maturation.

Adolescent↗

PubMed1985

Inhibitory action of exogenous melatonin, 5-methoxytryptamine, and 6-hydroxymelatonin on sexual maturation of male rats: activity of 5-methoxytryptamine might be due to its conversion to melatonin.

The effect on sexual maturation of 6 different pineal indoles, including melatonin, and of the metabolite 6-hydroxymelatonin was studied in the male rat after daily injections from 20 to 40 days of age. Only 5-methoxytryptamine (5MT) and 6-hydroxymelatonin (6M), in addition to melatonin, inhibited the neuroendocrine-reproductive axis during sexual maturation. Their potencies when injected in the afternoon were in the range of one-twentieth to one-fifth that of melatonin. Like melatonin these two indoles had no effect when injected in the morning. N-acetylserotonin, serotonin, 5-hydroxytryptophol and 5-methoxytryptophol did not influence sexual maturation either when injected in the morning or in the afternoon. Chromatographic separation was performed on plasma extracts from rats injected daily with the biologically active indoles and killed 10-120 min after the last injection. This procedure confirmed that 6M injections did not increase plasma melatonin levels. In contrast, plasma melatonin levels in 5MT-treated rats were increased 1 h after the 5MT injection. These results suggest that 5MT or part of it might be acetylated to melatonin; thus inhibition of sexual maturation might be mainly due to melatonin. These results indirectly support the contention that melatonin is the principal pineal indoleamine playing a role during sexual maturation.

5-Methoxytryptamine↗

PubMed1985

Daily administration of melatonin delays rat vaginal opening and disrupts the first estrous cycles: evidence that these effects are synchronized by the onset of light.

The effect of daily melatonin administration was investigated in the immature female rat. Starting on day 15 of age, 100 micrograms melatonin were injected sc at different times of the day in animals housed in 12 h of light, 12 h of darkness or 16 h of light, 8 h of darkness. Melatonin given 9-11 h after the onset of light in both lighting regimens resulted in a 10-day delay of vaginal opening, a dissociation of the relation between vaginal opening and first proestrus, and a disruption of the initial estrous cycles. The same dose of melatonin given at other times during the photoperiod had no effect on sexual maturation. GnRH secretion in melatonin-treated animals was decreased, as judged by 30% lower pituitary GnRH receptor number in animals killed after opening of the vagina. During the diestrous phases, plasma levels of LH, FSH, and 17 beta-estradiol were similar to those in control rats, but during proestrus, the surge of FSH was higher, and the peak of estradiol was higher and of a longer duration. This hormonal pattern suggests a build-up of hormones in secreting cells, which follows the lower incidence of proestrous phases in melatonin-treated rats. This build-up of FSH was indeed present, with higher concentrations in the pituitary during diestrus after melatonin treatment, while pituitaries removed during proestrus had lower contents of FSH. These results confirm that chronic melatonin administration delays sexual maturation of female rat, probably by retarding maturation of hypothalamic GnRH-producing cells. Thus, melatonin could modify basal GnRH secretion or pulsatile release. Pituitary and ovarian responsiveness do not seem to be affected, since proestrous surges of 17 beta-estradiol, LH, and FSH occur, albeit at a reduced frequency. The results also show that there is a window of maximum sensitivity to administration of melatonin 9-11 h after the onset of light, and that this window of sensitivity is synchronized by the onset of light. This raises the possibility that the abnormal presence of endogenous melatonin during this period of the day could induce abnormal sexual development.

Animals↗

PubMed1984

Influence of gonadoliberin on the differentiation of rat gonadotrophs: an in vivo and in vitro study.

The influence of gonadoliberin (GnRH) on the differentiation of rat gonadotrophs in early fetal life was studied both in vivo and in vitro by immunocytology with anti-porcine luteinizing hormone beta (pLH beta) serum. Adenohypophysial primordia explanted from 11 to 13 days of gestation were maintained in organ culture in synthetic Parker's 199 medium enriched with insulin (0.5 microgram/ml) and transferrin (5 micrograms/ml). Cultures lasted to approximate the usual gestation period (21 days). Synthetic GnRH (10(-9) or 10(-12) M) was added to the culture medium during the first day of culture only. In contrast to a previous report, immunoreactive cells were detected in the primordia explanted either at 11 or 12 days of gestation only when cultured in the presence of GnRH. The appearance of positive localization was seen by 17 days. No differences due to GnRH dosage were observed in the mean cytoplasmic area of the cells in the different experimental groups as seen at the equivalent of 21 days. GnRH was not effective in a medium deprived of insulin. GnRH, added 6 h before the end of the culture, could also release the secretory product of gonadotrophs which recently developed the presence of immunoreactive pLH beta material. In these conditions, GnRH was shown to enter the cells as observed by immunocytochemistry on sections obtained after cryoultramicrotomy. Endogenous GnRH was also detected by the same technique in fetal pituitary glands removed from 14 to 21 days of gestation. It was always localized in agranular cells and from 18 days in some granular cells considered as gonadotrophs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗