Biomedical subjects

M L Aubert

Publications and source records attributed to M L Aubert.

At least 55 records · Page 3Linked to original sources

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

Effects of early undernutrition and handling on the adrenocortical activity of neonatal rats.

Early neonatal experiences such as handling or undernutrition may alter developmental patterns associated with brain maturation and neuroendocrine regulation. Therefore, we tested neonatal ACTH and corticosterone responses to ether stress in pups submitted to chronic underfeeding which involves daily handling (U), daily handling only (H), or no handling (I). Pituitary ACTH content and brain myelin basic protein (MBP) content were measured in all rat groups. We found that the order of magnitude in stress-induced ACTH secretion was: I greater than H greater than U on day 14 and 18 of age while on day 10, only a small significant response in the H group was observed. Corticosterone secretion after stress was increased on day 14 in both H and I rats while no response was observed in the U group at all ages. Pituitary ACTH content of U pups was significantly (p less than 0.01) reduced compared to H rats on day 10 of age but not later. Underfeeding had profound effects on MBP synthesis of U rats since brain MBP content on day 14 was 5-fold lower in U versus H pups. In addition, handling enhanced MBP production since H rats exhibited higher (p less than 0.05) MBP content as compared to I rats. Thus, both handling and undernutrition experienced early in life are able to affect central brain maturation as well as neonatal adrenocortical responses to stress.

Adrenal Cortex↗

PubMed1988

Purification of PRL receptors from toad kidney: comparisons with rabbit mammary PRL receptors.

The binding characteristics of the prolactin (PRL) receptors present in toad (Bufo marinus) kidneys were investigated and compared to those of PRL receptors present in rabbit mammary glands. The molecular characteristics of the Triton X-100 solubilized renal and mammary PRL receptors were assessed by gel filtration and by migration analysis on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) after affinity labeling of the binding sites with 125I-human growth hormone. Similar results were obtained for both receptors. Partial purification of the toad PRL receptor could be achieved by affinity chromatography. The molecular weight of this purified receptor could be determined by analysis on SDS-PAGE. With the use of a polyclonal antiserum raised against a purified preparation of rabbit mammary PRL receptor, one or several antigenic epitope(s) could be identified on the core of the toad renal PRL receptor. In conclusion, although the structure and the biological role(s) of PRL have substantially changed during evolution, the receptor for this hormone has retained many of its structural features as could be assessed between an amphibian and a mammalian species on functionally different target tissues.

Affinity Labels↗

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

Differentiation of fetal rat somatotropes in vitro: effects of cortisol, 3,5,3'-triiodothyronine, and glucagon, a light microscopic and radioimmunological study.

Cortisol stimulates somatotrope differentiation in vitro. T3 and/or glucagon may also be involved. Fetal rat pituitary primordia were explanted at 14 days gestation and cultured for 7 days in medium supplemented with cortisol (50-500 nM), and either T3 (0.67 nM) or glucagon (0.5 nM). Also, to determine the time of first appearance of the somatotropes, explants were cultured 4, 5, or 6 days with cortisol alone. Immunoreactive somatotropes were detected by immunohistochemistry, and their size and number were estimated for each medium. GH was measured by RIA in explants and media. Immunoreactive somatotropes first appear at 18-19 days gestation. Their size and number depend on cortisol concentration: no cells at 50 nM, a few small ones at 100 nM, and many large ones at 250-500 nM. This progression was reflected by RIA of GH in explants and media, although small quantities were detected with 50 nM. The effect of T3 was only visible with a low dose of cortisol. With 100 nM cortisol, it increased the size and number of cells. Differentiation was also triggered with 50 nM cortisol plus T3. RIA detected significantly higher GH content and secretion after T3 stimulation. The decreases in number, size, and GH secretion and content elicited by glucagon were not significant, probably due to the high variability. Both techniques used provide similar information on somatotrope differentiation: stimulation by cortisol alone, or alternatively by a synergistic action between cortisol and T3.

Animals↗

PubMed1987

Binding and internalization of native gonadoliberin (GnRH) by anterior pituitary gonadotrophs of the rat. A quantitative autoradiographic study after cryoultramicrotomy.

To identify anterior pituitary cell types containing GnRH binding sites and to study the internalization process of this peptide by target cells under physiological conditions, autoradiography was performed on rat anterior pituitaries removed at specific time intervals (2-60 min) after intravenous injection of mono-radioiodinated 125I-GnRH into intact males. At electron-microscopic level, gonadotrophs and lactotrophs appeared to contain silver grains. Concomitant administration of an excess of unlabeled GnRH with the radioiodinated hormone prevented this localization indicating the specificity of the reaction. The time-course study in gonadotrophs showed that 2 min after injection silver grains could be found over the plasma membrane, secretory granules and nuclear membrane. Similar results were observed 5 and 15 min after injection. Extensive label was observed over the nucleus and nuclear membrane 15 to 60 min after injection. The injection of a radioiodinated GnRH agonist [D-Trp6, Pro9 (Net), DesGly10]-GnRH produced comparable results. In contrast, the injection of 125I-[D-pGlu1, D-Phe2, Trp3,6]-GnRH, an antagonist of GnRH, produced positive labeling only at the plasma membrane without internalization. These results indicate that, after binding with receptors on the plasma membrane, GnRH is rapidly internalized, accumulating in secretory granules, and localizing over the nuclear membrane and later, in the nucleus. Association of radioactivity with secretory granules could be related to a specific action of GnRH at this level or to receptor recycling, and presence of label in the nucleus may be related to stimulation of neosynthesis of LH and GnRH receptors.

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

Pharmacodynamics of [D-Ser (t-Bu)6,Des-Gly10]GnRH ethylamide (Buserelin) in 6 normal volunteers. Its usefulness to monitor treatment of central precocious puberty.

The disappearance rate of [D-Ser(t-bu)6,des-Gly10]GnRH ethylamide (Buserelin, HOE 766) was studied in plasma and urine after intranasal (300 micrograms) or sc (10 micrograms/kg) administration. A radioimmunoassay for HOE 766 was developed using 125I[D-Trp6,Des-Gly10]GnRH ethylamide as tracer and an antiserum raised against HOE 766. Cross-reaction with native GnRH was only 1.7%. Sensitivity was 1 pg/tube. In 6 male adolescents, the mean plasma HOE 766 concentration (+/- SEM) was 0.46 +/- 0.08, 0.50 +/- 0.10, 0.28 +/- 0.04, 0.24 +/- 0.04, 0.13 +/- 0.03, and 0.08 +/- 0.02 micrograms/l 30, 60, 90, 120 and 180 min after the intranasal administration, respectively. Concomitant urinary excretion of HOE 766-like material was 9.43 +/- 1.96 micrograms/4 h. There was a good correlation between integrated plasma levels and urinary excretion (r = 0.92). In the same 6 volunteers, the plasma HOE 766 levels were 21.2 +/- 3.0, 25.9 +/- 0.8, 21.2 +/- 0.9, 17.1 +/- 0.7, 12.8 +/- 1.1, 8.9 +/- 0.4, and 5.9 +/- 0.8 micrograms/l 20, 40, 60, 90, 120, 180 and 240 min after sc injection, respectively. The mean urinary excretion was 543 +/- 61 micrograms/4 h. In two girls with precocious puberty treated during 12 to 15 months with intranasal administration of HOE 766, urinary excretion of HOE 766-like material was shown to correlate well with the degree of inhibition of plasma 17 beta-E2 and of plasma LH and FSH responses to a GnRH challenge. Thus, monitoring of HOE 766 in urine appears to be helpful for evaluating of intranasal therapy with a GnRH analog in precocious puberty.

Administration, Intranasal↗

PubMed1987

[Differentiation of pituitary cells in culture].

Gonadotrophs were first detected at 18 days of gestation in normal rat fetus. Encephalectomy performed at 16 days of gestation did not modify the normal aspect of cells at term. In adenohypophysial primordia explanted from 13 days of gestation differentiated gonadotrophs were detected after culture (8 days) in medium containing insulin (minimal dose required: 0.5 microgram/ml) and transferrin (5 micrograms/ml). In contrast, in primordia explanted at 11 and 12 days of gestation, GnRH 10(-9) to 10(-12) M was required for the first 24 hours of culture to induce differentiation of cells which was obtained in synergy with insulin and transferrin. On the other hand, fetal hypothalamic GnRH and pituitary GnRH receptors were observed from 12 days of gestation which can explain the observations made on primordia explanted at 13 days. Lactotrophs first appeared at term in normal rat fetus. In vitro, differentiation of lactotrophs was not observed in primordia explanted from 13 days in the presence of insulin and transferrin alone, but it was induced by GnRH (10(-9) M) for the 24 hours of culture in the same medium. The action of GnRH was mediated through glycoproteins and specifically isolated alpha subunit. Indeed, purified LH alpha-subunit added in medium instead of GnRH induced differentiation of lactotrophs from 10(-9) M with an increase in the number of cells related to the dose of hormone. Differentiation of the two cell types is very linked in these culture conditions. Gonadotroph differentiation is regulated by an hypothalamic endocrine secretion whereas lactotroph differentiation is more dependent on a paracrine secretion.

Animals↗

PubMed1986

Structure-function studies on human growth hormone. Evidence that tertiary structure is essential for biological activity.

The relationship between the conformation of human pituitary growth hormone (hGH), biological activity, and ligand binding activity was studied by comparing conformational details previously published on in vivo and in vitro studies of identical samples of hGH and its known derivatives. In vivo assays included the rat tibia test for somatotropic activity and the pigeon crop-sac assay for lactogenic hormone activity. Relative binding affinities were compared in radioimmunoassays using 125I-hGH as tracer with 1) anti-human chorionic somatomammotropin (hCS) serum (low discriminatory hybrid assay), 2) anti-hGH sera (in conventional assays), 3) monospecific anti-hGH serum (absence of cross-reaction with hCS) and 4) human anti-hGH sera obtained from GH-deficient patients on replacement therapy. In addition, binding affinities were examined in two receptor-binding assays, one specific for somatotropic activity (rabbit liver membranes, 125I-hGH), and the other, for lactogenic hormones (rabbit mammary membranes, 125I-oPRL). The conformational properties of native hGH and various chemically and enzymatically modified derivatives of the hormone were evaluated primarily from circular dichroism spectra, while conformational stabilities were estimated from the relative rates of tryptic digestion. Unfragmented, but chemically modified derivatives, exhibited good parallelism between retention or loss of native conformation and the in vivo potencies and in vitro binding affinities. None of the fragments of hGH showed activity in any of the radioreceptor assays or radioimmunoassays. Two derivatives of hGH, which contain gaps of 6 or 12 residues in the polypeptide backbone produced by partial enzymatic digestion, had full or increased in vivo potencies, full activities in the radioimmunoassays, and were the most active derivatives in both radioreceptor assays. One of these, missing the hexapeptide corresponding to residues 135-140, was also found to retain nearly all the conformational properties of native hGH. These studies proved further evidence that 1) retention by modified forms of hGH of a high degree of in vivo biological potency or in vitro binding affinity is causally related to the retention of most of the conformation and conformational stability of the molecule, and 2) the biologically active, receptor-binding and immunoreactive sites on the hGH molecule are 3-dimensional in nature.

Animals↗

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↗

PubMed1986

Neuroendocrine changes characteristic of sexual maturation.

A general scheme of neuroendocrine factors influencing the onset of puberty is presented. Gonadotropin-releasing hormone (GnRH) is secreted in pulsatile fashion by the arcuate nucleus of the hypothalamus. Amplitude and probably frequency of the secretory pulses of GnRH increase at the time of puberty, stimulating the secretion of pituitary gonadotropins (LH and FSH). In turn, the gonadotropins induce the maturation of the ovarian follicles in the girls, spermatogenesis in the boys, and the secretion of estradiol or testosterone. The increase of the pulsatile secretion of GnRH is sufficient for explaining the onset of puberty. The response of the pituitary gonadotropins to GnRH would depend on the presence of sex steroids through the feedback mechanisms. The secretion of GnRH may be influenced by neurotransmitters. Norepinephrine, epinephrine and dopamine would stimulate GnRH secretion. Such effect, in fact, depends on the steroid milieu. Opposite effects can be observed in absence of estradiol. Serotonin has a negative effect on the GnRH secretion. Melatonin appears also to block GnRH secretion at the time of puberty. Finally, beta-endorphins decrease the frequency of GnRH secretion only in the presence of steroids. It is probable that stress and underweight act in blocking the pubertal development through the action of neurotransmitters, in particular catecholamines and beta-endorphins.

Adolescent↗

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

Specific binding sites for ovine prolactin in three amphibian cell lines.

Established cell lines (TB-6c and TB-M) obtained by continuous culture of epithelial cells from toad Bufo marinus urinary bladder, which, in culture, maintained a high degree of functional differentiation, exhibited a significant number of high-affinity (KA = 1-2 X 10(10) M-1) binding sites detected both with radioiodinated (125I) ovine prolactin (oPRL) and human growth hormone (hGH). Binding capacity was higher in the case of TB-6c cells (7,573 +/- 581 sites/cell) than with the TB-M cells (1,160 +/- 87). Similarly, binding sites for oPRL were characterized on Xenopus laevis kidney-derived cell line A6. With oPRL used both as tracer and standard, significant cross-reaction was observed with hGH, less with human or rat prolactin (PRL), and none with human chorionic somatomammotropin, bovine growth hormone, and rat luteinizing hormone or follicle-stimulating hormones. B. marinus pituitary extracts completely displaced the binding of 125I-oPRL to toad bladder binding sites. This finding of specific sites for PRL on amphibian bladder and kidney cells confirms that PRL exerts specific biological actions for the control of electrolyte and water metabolism in the amphibians.

Animals↗

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↗

PubMed1985

Ontogeny of hypothalamic luteinizing hormone-releasing hormone (GnRH) and pituitary GnRH receptors in fetal and neonatal rats.

Although it is known that LH secretion starts at 17 days of gestation in the fetal rat and that this first LH release is most likely driven by hypothalamic GnRH, an earlier role for GnRH during fetal life has been postulated with the observation that presence of GnRH is important before day 13 of gestation for the differentiation of the pituitary anlage. In order to clarify the different roles of GnRH during fetal life, we have studied the first appearance of GnRH in the fetal brain, the expression of GnRH receptors in the fetal pituitary gland, and the presence of GnRH immunoreactivity within the fetal gonadotrophs. GnRH was present in the earliest brain tissue examined (12 days of gestation). From 12-17 days, GnRH content of fetal brain remained low and then increased markedly by the end of gestation. No immunoreactive GnRH-like material could be detected in rat placental tissue throughout gestation. Binding sites for GnRH were detected as early as 12 days of gestation in fetal pituitary glands. However, binding was very low until 16 days. At 17 days, Scatchard analysis indicated the presence of high affinity, low capacity binding sites [affinity constant (Ka) = 10(10) M-1]. Intracellular presence of GnRH as seen by immunocytochemistry using ultrathin sections prepared by cryoultramicrotomy was first visible at 14 days and started to increase at 16 days. LH was first detectable in the fetal pituitary by RIA at 17 days; FSH was first detectable at 21 days, and PRL at 1 day of postnatal life. Thereafter, neonatal pituitary contents of LH, FSH, and PRL increased linearly with-time, as did the number of pituitary GnRH receptors. At 10 days of postnatal life, pituitary contents of LH and FSH were significantly higher in females than in males. In summary, hypothalamic GnRH appears early in fetal life and potentially can induce differentiation of the pituitary anlage. Conversely, the presence at 15 days of gestation of specific binding sites for GnRH and of intracellular GnRH immunoreactivity in gonadotrophs indicates that the hypophysiotropic action of GnRH clearly precedes the start of LH biosynthesis.

Animals↗