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M L Aubert

Publications and source records attributed to M L Aubert.

At least 37 records · Page 2Linked to original sources
PubMed1997

Identification of high-potency neuropeptide Y analogues through systematic lactamization.

In the pursuit of potent analogues of neuropeptide Y (NPY) that are selective for the Y1 receptor subtype, two lactam bridge scans of a centrally truncated parent compound were synthesized. A single lactam bridge (gamma-carboxyl of Glu to epsilon-amino of Lys) extending from residues i to i + 3 or i to i + 4 of the proposed alpha-helical region (residues 25-31 of NPY) was introduced in des-AA7-24[Gly6]NPY. Cyclogues (contraction of cyclic analogues), which were approximately one-half the size of native NPY, were initially screened for binding affinity at two discrete NPY receptor types using human neuroblastoma cell membranes, SK-N-MC and SK-N-BE2. Exploitation of the subtle differences present on each receptor type allowed for the identification of cyclogues which bound specifically to Y1 receptors with increased affinity when compared to the corresponding linear parent analogue, while one short Y1 specific cyclogue, des-AA2,3,5,7-24cyclo-(26/29)[Gly6,Glu26,Lys2 9,Pro34]NPY, bound with Ki = 16 nM. Other cyclogues showed distinct preference for Y2 receptors and bound in the low-nanomolar range. Functionally, the compounds inhibited the norepinephrine-stimulated accumulation of cAMP indicating that all acted as agonists with varying potencies.

Amino Acid Sequence↗
PubMed1997

Effects of constant infusion with insulin-like growth factor-I (IGF-I) to immature female rats on body weight gain, tissue growth and sexual function. Evidence that such treatment does not affect sexual maturation of fertility.

Plasma levels for insulin-like growth factor-I (IGF-I) steadily increase in female rats between 20 and 40 d of life, and this increase is intimately related to the wellknown growth spurt occurring at this age. Since specific actions of IGF-I related to sexual function have been described at the ovarian and hypothalamic levels, an endocrine role of rising circulating IGF-I levels during sexual maturation cannot be excluded. Therefore, the impact of adult-type plasma IGF-I levels during the juvenile age, on body weight (BW) gain, growth of several organs, sexual development, and fertility has been evaluated. Female Sprague-Dawley rats were infused with rhIGF-I (2 and 4 micrograms/g BW/d, using Alzet minipumps), between 20 and 41 d of life. When infusing 2 micrograms/g BW/d, plasma levels for IGF-I were increased 1.5- to 2-fold over controls at all ages studied. They were further increased with the higher dosage, but only after 35 d of age. Plasma levels for insulin-like growth factor binding protein (IGFBP)-1 to -3 were clearly increased. BW gain was significantly increased, but only with the higher dosage. Tail length was never modified. In contrast, a growth acceleration for spleen, kidneys, adrenals, and ovaries was observed with both dosages. The ovarian weight of treated animals represented approx 140% of control animals with the 4 micrograms/g BW/d dosage. Histology of the enlarged ovaries did not reveal any abnormalities. No meaningful modification of the timing of vaginal opening was observed, and fertility was not comprised by previous rhIGF-I infusion during 20-41 d age period. In summary, early exposure to increased (adult-like) plasma IGF-I levels did not modify BW gain or tail length, but affected the development of spleen, kidneys, adrenals, and ovaries. Exposure to supraphysiological plasma IGF-I levels (> 1200 ng/mL), accelerated BW gain and increased the weight of all organs studied. No signs of precocious sexual maturation were seen and fertility was normal. In conclusion, prematurely increased plasma IGF-I levels affected somatotropic parameters, but not the onset of sexual function.

Animals↗
PubMed1996

Chronic administration of neuropeptide Y into the lateral ventricle inhibits both the pituitary-testicular axis and growth hormone and insulin-like growth factor I secretion in intact adult male rats.

Neuropeptide Y (NPY) is known to be involved in the central regulation of appetite, sexual behavior, and reproductive function. Whereas central administration of NPY strongly stimulates feeding in satiated animals, diet restriction or other unfavorable metabolic situations, such as diabetes, produce enhanced NPY gene expression and NPY release in the hypothalamus. Numerous studies have indicated that acute central administration of NPY results in various actions on LH secretion in the rat, either stimulatory or inhibitory. We recently demonstrated that chronic infusion of NPY into the lateral ventricle of adult intact female rats profoundly inhibited both the gonadotropic and somatotropic axes, with disruption of estrous cyclicity. Furthermore, we showed that central chronic infusion of NPY delayed sexual maturation in female rats. To analyze the effects of the same type of chronic NPY treatment on the pituitary-testicular axis, 45-day-old Sprague-Dawley male rats were implanted with stainless steel cannulas in the right lateral ventricle. Ten days later, Alzet osmotic minipumps were filled with different NPY solutions, adjusted to deliver 6, 18, or 36 micrograms/day, connected to the intracerebroventricular (icv) cannula, and sc implanted dorsally. The effects of these treatments were evaluated over 7 days. In one case, rats were castrated 5 days after initiation of NPY treatment, and the effect of castration was evaluated 2 days later. Chronic icv infusion of NPY produced the expected dose-related increases in food intake from 33.0 +/- 0.9 (basal) to 53.4 +/- 3.3 g/day (18 micrograms NPY/day) and body weight gain (5.7 +/- 0.7 to 10.5 +/- 1.2 d/day). As in female rats, this orexigenic action of NPY resulted in a significant dose-related decrease in pituitary weight, from 12.4 +/- 0.7 to 9.9 +/- 0.4 mg. The 7-day NPY infusion produced highly significant decreases in seminal vesicle weight (853 +/- 77 to 230 +/- 31 mg) and testis weight (3.82 +/- 0.09 to 3.18 +/- 0.15 g; P = 0.003). Plasma levels of testosterone (231 +/- 71 to 48 +/- 13 ng/dl), LH (20.7 +/- 3.7 to 9.1 +/- 1.2 ng/ml), and FSH (282 +/- 17 to 190 +/- 18 ng/ml) were markedly decreased at the 18 micrograms/day dosage, as also demonstrated for the 36 micrograms/day dosage. None of these effects was observed if vehicle was infused into the lateral ventricle instead of the NPY solution. When bilateral orchidectomy was performed 5 days after initiation of the NPY infusion (18 micrograms/day), the immediate LH and FSH rises usually seen after castration were seriously blunted.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Chronic administration of neuropeptide Y into the lateral ventricle starting at 30 days of life delays sexual maturation in the female rat.

The role of neuropeptide Y (NPY) in the regulation of sexual function is still controversial. Whereas central NPY administration is stimulatory during proestrus in the rat and other species, such administration is inhibitory in castrated animals and we have shown that chronic, central infusion of NPY inhibits both the gonadotropic and somatotropic axis in adult rats. Previous studies have suggested that NPY could be involved in the triggering of the first ovulatory LH surge and a recent report indicated that a single central NPY injection given at 30 days of life could advance sexual maturation. We therefore evaluated the effect of chronic NPY administration on the timing of sexual maturation in the female rat and compared the effects obtained with those induced by a single NPY injection. Constant infusion of NPY (18 micrograms/day) into the lateral ventricle delayed sexual maturation as seen by the absence of vaginal opening, delayed ovarian growth and reduced number of pituitary GnRH receptors. This inhibitory effect was seen as long as NPY was infused. In contrast, a single NPY injection either at 30 days of life or earlier, or repeated single injections between 28 and 31 days of life, did not modify the pace of sexual maturation. Unlike what is observed in adult animals, overall food intake was only minimally increased between 30 and 37 days of life in chronically NPY-infused rats, but this increase became more important thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1995

[Effect of gonadotrophins, testosterone and growth hormone on spermatogenesis in two hypophysectomy patients].

Human chorionic gonadotrophin (hCG), human menopausal gonadotrophins (hMG) and somatotrope hormone (STH) were used for three months to induce spermatogenesis in a patient with azoospermia following hypophysectomy for Cushing's syndrome. Azoospermia reappeared when testosterone was substituted for hCG, despite continued treatment with FSH and STH. In a second patient who had undergone hypophysectomy for a craniopharyngioma presenting residual oligospermia, STH alone was uneffective in improving the sperm count. In both patients, the level of IGF-1 in seminal fluid was unchanged by STH despite increased serum IGF-1. The use of STH to induce spermatogenesis is discussed in light of its capacity to increase testosterone synthesis is response to hCG.

Adult↗
PubMed1994

Cyclic AMP increases the release of parathyroid hormone-related protein from a lung-cancer cell line.

Parathyroid hormone-related protein (PTHrP) plays an important role in the pathogenesis of malignant hypercalcemia by stimulating bone resorption and/or renal tubular reabsorption of calcium. In cultured cancer cells, its production can be influenced by various factors or ions, but the regulation of its production is still poorly understood. We investigated the effects of stimulators of cAMP synthesis on PTHrP release by a human lung squamous-carcinoma cell line (BEN). In superfused cells grown on microcarrier beads, PTHrP production was significantly increased after incubation with calcitonin for only 20 min. The release of immunoreactive and bioactive PTHrP was increased by incubating the cells with forskolin, 3-isobutyl-1-methylxanthine or dibutyryl cAMP even in the presence of the protein-synthesis inhibitor cycloheximide for 6 hr. The calcitonin-mediated stimulation was not accompanied by concomitant changes in PTHrP mRNA. The microfilament-disrupter cytochalasin D was shown to enhance the basal and calcitonin-induced production of PTHrP. These results indicate that stimulators of cAMP synthesis enhanced PTHrP release by BEN cells.

1-Methyl-3-isobutylxanthine↗
PubMed1994

Intracellular gonadotropin-releasing hormone immunoreactivity in gonadotrophs of intact or castrated male rats: semiquantitative estimation of testosterone and GnRH antagonist treatment.

Changes in intracellular gonadotropin-releasing hormone (GnRH) immunoreactivity (GnRH-IR) in pituitary gonadotrophs were assessed by the use of a semiquantitative immunocytochemical method in male rats undergoing various manipulations known to greatly modify gonadotropin secretion. In basal conditions, immunoreactive GnRH was localized in the cytoplasmic matrix, the secretory granules and the nucleus of these cells. Following intravenous stimulation with GnRH (100 ng i.v.), the GnRH-IR increased rapidly in all these three subcellular compartments, peaking at 15 min. In untreated, long-term castrated rats, GnRH-IR increased both in the basal state and after administration of GnRH. Injection of the castrated rats with testosterone propionate reduced the observed GnRH-IR to the level observed in intact rats. Acute or chronic treatment of castrated rats with a potent GnRH antagonist rendered GnRH-IR completely undetectable in all the three previously positive subcellular compartments of gonadotrophs, and GnRH-IR did not reappear after stimulation with GnRH. In sum, the fact that modifications of GnRH immunoreactivity are observed in rat gonadotrophs: (1) confirms the GnRH internalization process; (2) suggests different sites of action for GnRH within the cell, and (3) demonstrates rapid clearance of intracellular GnRH after stimulation.

Animals↗
PubMed1994

Binding kinetics of the long-acting gonadotropin-releasing hormone (GnRH) antagonist antide to rat pituitary GnRH receptors.

The GnRH antagonist Antide has been shown to produce prolonged inhibition of gonadotropin secretion in ovariectomized monkeys and other animal models. The reasons for such a long duration of action have not yet been clarified. To understand the mode of action of this new antagonist, we have performed association and dissociation binding kinetics using either crude rat pituitary homogenates as source of GnRH receptors or dispersed pituitary cells in culture. The binding characteristics of the radioiodinated Antide analog 125I-labeled[D-Tyr0] Antide to GnRH receptors in rat pituitary homogenates were comparable to those of the first generation GnRH antagonist 125I-labeled [Ac(3)Pro1,pFD-Phe2,D-Trp3,6]GnRH or the GnRH agonist 125I-labeled [D-Trp6,(N-Et)Pro9,Des,Gly10]GnRH, with an affinity constant (Ka) in the 10(10) M-1 range. The maximum binding capacity was consistently higher with the antagonist tracers than with the [125I]GnRH agonist. Both antagonists dissociated at a slower rate at 4 C (approximately 4 times) than the [125I]GnRH agonist. Incubation at 23 C of 125I-labeled [D-Tyr0] Antide previously bound at 4 C resulted in complete dissociation within 8 h after the addition of an excess amount of any of the GnRH analogs; in addition, simple dilution of the incubation medium produced spontaneous dissociation at this temperature. Using rat pituitary cells, Antide was found to inhibit the LH response to native GnRH (10(-8) M) in a dose-related manner. To test whether the binding of Antide is normally reversible at 37 C, Antide (10(-7) M) was added to the culture medium 3 days after cell plating, and the initial preincubation was resumed for 24 h. Cells were then washed twice, and dissociation was allowed to take place. Bound Antide was shown to dissociate rapidly at 37 C, as cells previously treated with Antide produced a full LH response within 24 h if challenged with native GnRH. In conclusion, the binding kinetics of 125I-labeled [D-Tyr0]Antide to GnRH receptors, which should reflect those of Antide, did not present abnormal features. Although this antagonist, similar to other GnRH antagonists, dissociated from pituitary receptors at a slower rate than GnRH analogs, rapid and spontaneous dissociation was achieved at 23 C with simple dilution, and dissociation of unmodified Antide occurred at 37 C. Taken together, our results support the concept that the long duration of action of Antide is not due to any toxic effect of Antide at the receptor site and could derive only marginally from the slow dissociation rate of this antagonist.

Animals↗
PubMed1994

Growth hormone (GH) deprivation induced by passive immunization against rat GH-releasing factor does not disturb the course of sexual maturation and fertility in the female rat.

The importance of normal GH secretion for the onset of sexual maturation is a subject of controversy. Also, the need to achieve a minimal body size or body fat content has been postulated to be of importance for determining the timing of the onset of puberty. To evaluate the importance of GH secretion on the onset of sexual maturation in the female rat, GH deprivation has been induced by treating prepubertal rats with antirat GRF serum to passively immunize these animals against GRF. Chronic administration of anti-GRF serum produced in all series an impressive reduction in growth rate (from 5 to 2 g/day), resulting in a body weight averaging 50-60% the normal value at 50 days of life. Despite this deficit in growth, sexual maturation, as established by vaginal opening and first estrous cycles, occurred at the normal age in three of four series of rats; in one series, however, sexual maturation was delayed by 4 days, but thereafter, all parameters indicated that the gonadotropic axis was normally activated. In one series, fertility was tested at 59 days of age in females with a body weight corresponding to 51% of the control weight; these females conceived and delivered a reduced number of pups (9.4 +/- 0.7 instead of 14.2 +/- 0.8 in control dams), but the pups were of normal size. In a second experimental approach, the effect of GH deprivation was evaluated in a model of late sexual maturation obtained by severe food restriction followed by a switch to ad libitum feeding. Severe food restriction initiated at approximately 28 days, when the body weight was 75 g, drastically reduced the growth rate and completely prevented sexual maturation. A switch to ad libitum feeding at 50 days provoked an important compensatory growth and the occurrence of sexual maturation 4 days later. Passive immunization against GRF during this recovery phase did reduce the growth rate, but did not delay sexual maturation. Plasma insulin-like growth factor-I (IGF-I) secretion was very low in food-restricted rats and in each situation with induced GH deprivation. During food restriction, plasma IGF-binding protein-3 (IGFBP-3) and to a lesser extent IGFBP-1 were decreased, and IGFBP-2 was increased; after switching to ad libitum feeding, plasma levels of IGFBP-2 normalized, but levels of IGFBP-1 and IGFBP-3 remained low in the face of normalized plasma IGF-I levels.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Neuropeptide Y administered chronically into the lateral ventricle profoundly inhibits both the gonadotropic and the somatotropic axis in intact adult female rats.

Neuropeptide Y (NPY) is known to be involved in the central regulation of appetite, sexual behavior, and reproductive functions. Whereas central administration of NPY strongly stimulates feeding in satiated animals, diet restriction produces overexpression of NPY in the arcuate and paraventricular nuclei that might reflect behavioral adaptations to shortage of food. Previous studies indicated that central administration of NPY resulted in controversial actions on LH secretion, either stimulatory or inhibitory. In order to analyze the chronic effect on pituitary function of centrally administered NPY, stainless steel cannulae were implanted in the right lateral ventricles of intact 45-day-old Sprague-Dawley female rats. Ten days later, Alzet osmotic minipumps filled with saline or different concentrations of NPY adjusted to deliver 3, 6, 12, or 18 micrograms/day were connected to the intracerebroventricular (icv) cannulae, implanted sc dorsally, and the effects of these treatments evaluated after 7 days. Chronic icv infusion of NPY produced the expected dose-related increase in food intake [25.3 +/- 0.8 g/day (basal) to 47.9 +/- 4.3 g/day (highest NPY dose)] and body wt gain (3.7 +/- 0.4-11.5 +/- 1.4 g/day). Basal insulinemia was highly correlated to the increase in food intake. This orexigenic action of NPY was accompanied by a drastic dose-related decrease in pituitary wt (14.0 +/- 0.5-8.3 +/- 0.3 mg), pituitary concentration of GnRH receptors, a known marker of the activity of the hypothalamo-pituitary gonadal axis (15.2 +/- 1.7-5.2 +/- 0.5 fmol/mg), and ovarian wt (84.0 +/- 4.2-49 +/- 6.7 mg). Ovulation was impaired in NPY-treated animals as seen by daily inspection of vaginal smears. A sharp dose-dependent decrease in plasma levels of insulin-like growth factor I was also observed [934 +/- 64 ng/ml (basal) to 385 +/- 26 ng/ml (highest NPY dose)], probably secondary to a decrease in GH secretion. Whereas these data confirm the central action of NPY to stimulate appetite in satiated animals, they provide the first demonstration that chronic icv administration of NPY unequivocally inhibits gonadotropin secretion and sexual function in intact female rats. These data also confirm that NPY can suppress GH secretion and other anabolic hormones. In conclusion, these results may indicate a physiological role of NPY as an integrator of different adaptive behaviors in periods of unfavorable metabolic conditions such as diet restriction, extending its action to inhibition of sexual functions and anabolic processes.

Animals↗
PubMed1993

Evidence that neuropeptide Y could represent a neuroendocrine inhibitor of sexual maturation in unfavorable metabolic conditions in the rat.

Neuropeptide Y (NPY) is known to be involved in the central regulation of appetite, sexual behavior and reproductive function. Whereas central administration of NPY strongly stimulates feeding, diet restriction produces overexpression of NPY in the arcuate and paraventricular nuclei that might reflect behavioral adaptations to shortage of food. The role of NPY for the regulation of sexual function is still controversial. Whereas NPY is stimulatory during proestrus in the rat, acute administration of NPY is inhibitory in castrated animals and we have shown that chronic administration of NPY inhibits both the gonadotropic and somatotropic axis in adult female rats. In order to further analyse the role of NPY during sexual maturation, a model of delayed sexual maturation imposed by food restriction and return to ad-libitum feeding was used. Young female rats were restricted to 7-8 g food daily starting at 24 days of life (d). This restriction completely prevented sexual maturation. At 50 d, ICV cannulas were placed and at 60 d, Alzet minipumps either delivering NPY (18 micrograms/day) or vehicle into the ICV cannula were implanted dorsally. At 61 d, rats were switched to ad-libitum feeding, a change that produced vaginal opening within 4 days in all vehicle-treated rats. In the rats receiving NPY, significantly increased food intake and weight gain were observed but only one out of the 9 rats studied experienced vaginal opening at 66 d, the other 8 animals remaining sexually immature at 67 d at sacrifice. Sexual immaturity of NPY-treated rats was further confirmed by decreased ovarian weight and reduced number of pituitary GnRH receptors. Plasma IGF-I levels were markedly reduced in NPY-treated rats. Since food restriction has been shown both to increase hypothalamic NPY and to reduce or inhibit sexual function, these data bring evidence for the first time that NPY could be involved in the inhibition of sexual maturation imposed by food restriction, since maintenance of elevated NPY levels in the hypothalamus did prolong this state of sexual immaturity despite restoration of normal food intake.

Animals↗
PubMed1990

Reduction in testicular function in rats. I. Reduction by a specific gonadotropin-releasing hormone antagonist in fetal rats.

A gonadotropin-releasing hormone (GnRH) antagonist, when injected 24 h before sacrifice to rat fetuses, did not modify plasma testosterone concentrations in males on day 18 of gestation but it did on days 19, 20 and 21. This GnRH antagonist reduced plasma luteinizing hormone (LH) levels and increased pituitary LH content in both male and female 19-day-old fetuses from mothers adrenalectomized on day 14 of gestation. An inverse relationship between plasma testosterone and LH levels was noted in males and females, on days 19 and 21. These data suggest that the hypothalamic control of gonadotropic function is operating by day 19 of fetal life and that a negative feedback of testosterone on LH and probably GnRH release is also operating in rat fetuses on days 19 and 21 of gestation.

Adrenalectomy↗
PubMed1990

Reduction in testicular function in rats. II. Reduction by dexamethasone in fetal and neonatal rats.

Chronic administration of dexamethasone in drinking water to maternal rats from days 15 to 21 of gestation (1) reduced plasma testosterone concentrations in male fetuses between days 19 and 21 but not earlier on day 18 and abolished the prenatal peak of plasma testosterone which normally occurs on day 19 of gestation, and (2) suppressed the postnatal surge of plasma testosterone in male newborns 1.5 and 2 h after delivery at term by cesarean section. The administration of dexamethasone to male fetuses at birth induced 1 h later a slight but not significant increase in hypothalamic gonadotropin-releasing hormone (GnRH) and pituitary luteinizing hormone (LH) contents, reduced drastically plasma LH levels and completely prevented the postnatal surge of plasma testosterone which occurred normally in littermate controls. A rise in pituitary LH content, and a sharp reduction in plasma LH and testosterone concentrations were noted in 19-day-old male fetuses whose mothers were acutely treated with dexamethasone on day 18 of gestation. Similar evolutions for LH were observed in littermate females. These results suggest that the inhibitory effects of exogenous glucocorticoids on testosterone secretion could be mediated in both fetuses and newborns at least partially through suppression of the hypothalamic and pituitary secretion of GnRH and LH, respectively, and provide insight how stress or hormone imbalance may affect the development of this neuroendocrine system.

Animals↗
PubMed1990

Urinary excretion of [D-Ser(t-Bu)6,Des-Gly10]GnRH ethylamide (buserelin) during therapy of central precocious puberty: a multicentre study.

In order to compare the clinical effects of buserelin on central precocious puberty to its excretion in urine, as a parameter of metabolism or compliance, we have studied 52 patients treated either sc or intranasally. In girls with good control, urinary buserelin excretion represented 0.5 +/- 0.1% of the daily intranasal dose vs 12.5 +/- 2.3% of the daily sc dose. In boys, it represented 0.8 +/- 0.2 and 9.9 +/- 2.7%, respectively. In the sc treated group, 3 patients (2 girls and 1 boy) with poor control who exhibited excretion levels similar to those with good control were classified as resistant to therapy. Clinical control was poor in 4 intranasally treated girls: 2 had low excretion values suggesting poor compliance or failure of absorption by the nasal mucosa, and 2 appeared resistant to therapy, as urinary excretion levels of buserelin were similar to those of well-controlled patients. In addition, these data suggest that the small amount of buserelin absorbed by the nasal mucosa, as expressed by urinary excretion, is sufficient to desensitize the pituitary gonadotropes without any significant first-pass effect in the systemic circulation. This may explain the clinical effectiveness of the intranasal route for administration of small hormonal peptides acting on the pituitary gland.

Administration, Intranasal↗
PubMed1990

[Mechanism of action of gonadoliberin in pituitary gonadotropic cells].

The gonadotropin-releasing hormone (GnRH) controls LH and FSH secretion by membrane receptor interaction followed by a transmission mechanism involving Ca2+ secretion and phosphoinositides hydrolysis. In the first step, GnRH binds to its receptor and induces the formation of aggregates of a certain number of hormone-receptor complexes. Some of these GnRH-receptor complexes are internalized. Then, the receptors are either degraded in lysosomes or recycled through inclusion into secretory granules in the area of the Golgi. Note that receptor internalization is not necessary for the LH response to GnRH that intervenes immediately after GnRH binding to its receptor. Binding of GnRH to membrane receptors provokes extracellular calcium flux into the cell. At the same time, an increase in intracellular Ca2+ from non-mitochondrial stock is observed. Intracellular Ca2+ is important for the initiation of LH response and then extracellular Ca2+ is necessary for a sustained response. GnRH also stimulates phosphoinositides hydrolysis (probably mediated by a G-protein) inducing inositol 1,4,5-triphosphate liberation. This component would participate in Ca2+i increase necessary for the early LH response. Another hydrolysis product is diacylglycerol (DAG) that binds principally to protein kinase C (PKC). On the one hand, this complex can activate "masked" GnRH receptors and participate in this manner to an up-regulation. On the other hand, it seems that FSH beta mRNA expression depends on PKC. GnRH secretion rythm modulates alpha, LH beta and FSH beta subunits mRNA expression, and secretion of these hormones. PKC could be an important regulator of these functions. DAG can also induce LH secretion, this mechanism uses PKC activation and requires gonadotrophin neosynthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Modulation of the neonatal pituitary and adrenocortical responses to stress by thyroid hormones in the rat: effects of hypothyroidism and hyperthyroidism.

Neonatal rats exhibit a period of diminished pituitary and adrenocortical responses to stress during the first 2 weeks of life. Since thyroid hormones are known to affect brain development, modulation of these responses to stress by alterations in thyroid hormone status have been investigated in hypothyroid (Hypo) and hyperthyroid (Hyper) rat pups. Changes in ACTH and corticosterone (B) levels were measured under basal and stress conditions (3 min exposure to ether vapors) in neonates of various ages (day 5-21). Basal T4 and corticosterone-binding globulin (CBG) levels were also measured. Hypo pups were obtained from methimazole-treated mothers and hyperthyroidism was induced by daily subcutaneous injections of L-T4 (100 micrograms/kg BW) from birth on. In Hyper rats, premature onset of ACTH and B responses to stress was observed in 5-day-old rats while significant ACTH and B secretion only appeared by day 10 in vehicle-injected rats. By contrast, ACTH and B responses to stress were delayed in Hypo pups and only occurred by day 21. The lack of ACTH and B responses to stress of 14-day-old Hypo rats could be reversed by one single L-T4 injection (100 micrograms/kg BW) given 24 h, but not 4 h prior to exposure to stress. On day 21, smaller (p less than 0.05) stress-induced ACTH release was observed both in Hypo and Hyper rats compared to intact rats, concomitant with a diminished ACTH secretion following exogenous ovine CRF (10 micrograms/kg BW, i.p.) administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗
PubMed1989

Growth hormone (GH) deprivation induced by passive immunization against rat GH-releasing factor delays sexual maturation in the male rat.

GH deprivation after passive immunization against rat GRF (rGRF) markedly affects somatic growth in male rats. Since it has been postulated that GH and probably insulin-like growth factor-I (IGF-I) might have a permissive role on sexual maturation, the effects of GH deprivation on the course of sexual maturation were tested. Male rats were treated with a potent anti-rGRF serum between 15 and 39 days of life (0.25 ml administered sc every second day). Body weight of treated rats averaged 62% of that of control (normal rabbit serum-treated) rats at 40 days of life (d), and 64% at 50 d after which age, treated rats started to grow normally. At 40 and 50 d, pituitary GH content was very much depressed (representing approximately 20% of control values at both ages), plasma GH was undetectable, and plasma IGF-I levels averaged 30% of those of control rats. At 70 d, 30 days after cessation of treatment, pituitary GH content, and IGF-I secretion were almost normal. At 40 d, testes and seminal vesicles of treated rats were small-for-age in agreement with significantly decreased plasma levels of FSH and delayed spermatogenesis characterized by the presence of only few or no spermatozoa. At 50 d, 10 days after cessation of anti-rGRF injections, progress of sexual maturation was found to be consistent with age and coincided with normalization of growth rate. At 40 and 50 d, pituitary contents of FSH and LH were severely decreased but became normal at 70 d. In conclusion, GH deprivation which markedly affected somatic growth induced a transient delay of sexual maturation. GH deficiency seems to have affected mostly the synthesis and secretion of FSH, thus producing a delay in testes growth and in the differentiation of the germinal cells. The low levels of IGF-I might also have been the cause for the delay of maturation at the pituitary and/or the gonadal levels.

Animals↗