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PubMed1997

A critical period for thyroid hormone action on seasonal changes in reproductive neuroendocrine function in the ewe.

Thyroid hormones are obligatory for the annually recurring termination of reproductive activity in a spectrum of seasonal breeders, including sheep. Previous studies involving thyroidectomy and T4 replacement have led to the hypothesis that, in the ewe, thyroid hormones are necessary only during a limited interval late in the breeding season for the neuroendocrine processes that cause the transition to anestrus. The present series of experiments tested this hypothesis by assessing the influence of thyroidectomy, with or without T4 replacement for specific durations and at different times of the year, on the transition to anestrus. Seasonal alterations in reproductive neuroendocrine activity were monitored by changes in serum LH concentration in ovariectomized ewes bearing s.c. SILASTIC brand silicon tubing implants containing estradiol. Thyroidectomy in mid-December, just before the putative period of thyroid hormone action, prevented the development of the neuroendocrine anestrous season (fall in LH in this animal model). T4 replacement for 90 days beginning in late December (i.e., during the postulated period of thyroid hormone action) overcame the blockade of anestrus, causing LH to fall in ewes thyroidectomized several months previously. The minimal effective duration of exposure to thyroid hormones required for the transition to anestrus was estimated to be 60-90 days. Further, exposure to T4 for 60-90 days beginning in late December was found to be the only time of the year that thyroid hormones were required to maintain seasonal changes in reproductive neuroendocrine activity. Finally, replacement of T4 for 90 days at a different time of year (beginning in August) failed to provoke development of neuroendocrine anestrus in thyroidectomized ewes. These results support the hypothesis that thyroid hormones are necessary only during a limited interval late in the breeding season to promote seasonal reproductive suppression in the ewe. Further, the reproductive neuroendocrine axis is not equally responsive to thyroid hormone at all times of the year. This suggests there is a critical period of responsiveness during which thyroid hormones must be present for anestrus to develop.

Anestrus↗
PubMed1981

Relationship of hormones to inhibition of mammary tumor development by underfeeding during the "critical period" after carcinogen administration.

Seven days prior to 7,12-dimethylbenz(a)anthracene (DMBA) administration, virgin 50-day-old female Sprague-Dawley rats were placed on a food-restricted diet and continued on this regimen until 30 days after DMBA injection. One day prior to and 7 days after DMBA administration, animals were given daily 0.1-ml s.c. injections of 0.9% NaCl solution (controls), haloperidol (HAL; 0.5 mg/kg) to increase prolactin secretion, growth hormone (GH; 0.5 mg/kg), estradiol benzoate (EB; 1 microgram/rat), or a combination of HAL, EB, and GH. Drug and hormone treatments were terminated after 8 days, but underfeeding continued for 30 days after DMBA administration, after which time all animals were placed on ad libitum feeding for the remainder of the 26-week experiment. Food restriction for 7 days prior to and 30 days after DMBA administration resulted in a significant reduction in average tumor number and size by the end of the 26-week experiment. Treatment for 8 days with EB produced a significant increase in mammary tumor incidence despite underfeeding, whereas underfed rats given the combination of HAL EB, and GH showed development and growth of mammary tumors equal to that of full-fed controls. Both EB and HAL significantly raised blood prolactin levels. GH alone had no apparent effect on mammary tumor incidence. These results indicate that reduced food intake during the "critical period" for induction of mammary tumors in rats by DMBA can produce inhibition of mammary tumor development throughout the 6-month period of this experiment and that administration of EB or the combination of EB, HAL, and GH for only 8 days can counteract the inhibition by underfeeding.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1988

A critical period of the development of beta-adrenergic receptor binding in the visual system of rat during visual deprivation.

The density of [3H]dihydroalprenolol binding to beta-adrenergic receptors in the visual structures (visual cortex, superior colliculus and lateral geniculate nucleus) of rats raised under a normal 12 hr light-dark cycle was compared to those of rats visually deprived at different postnatal ages. Unilateral eyelid suture from postnatal days 10 or 16 to 3 months resulted in an increased [3H]dihydroalprenolol bilateral binding in the lateral geniculate nucleus compared to control animals. Monocular deprivation from postnatal days 25, 40, 60 and 90 had no effect on the density of [3H]dihydroalprenolol binding. After re-opening of the eyelid, which was sutured on postnatal day 10, at postnatal day 25 no changes in beta-adrenergic receptor binding in the lateral geniculate nucleus of the adult animal could be detected. After re-opening of the sutured eyelid on day 90, followed by examination of the adrenoceptor density 4 weeks later, the [3H]dihydroalprenolol binding in both lateral geniculate nuclei remained elevated as was also found in corresponding regions of monocular deprived animals. Binocular visual deprivation from postnatal day 10 until the age of 3 months had no effect on [3H]dihydroalprenolol binding in the visual centres in comparison to corresponding control animals. The data suggest that there exists a critical period for the ontogenetic development of beta-adrenergic receptors binding in the visual system of rats during which permanent alterations of receptor binding can be induced by monocular but not binocular visual deprivation.

Aging↗
PubMed2003

Comprehensive evaluation of the extraocular muscle critical period by expression profiling in the dark-reared rat and monocularly deprived monkey.

PURPOSE: To address the consequences of visual deprivation paradigms in rat (dark rearing) and monkey (monocular deprivation) on extraocular muscle (EOM) development using genome-wide expression profiling. METHODS: Serial analysis of gene expression (SAGE) was used to determine alterations in the EOM transcriptome induced by dark rearing of rats from birth to postnatal day 45. Data were compared with previously published normal EOM SAGE library. DNA microarray similarly assessed changes in gene expression patterns of EOMs of monkeys reared from birth to 4 months of age with monocular deprivation. RESULTS: Dark rearing produced changes in expression of 280 transcripts in rat EOM. Of these, 71 were known genes representing functional categories that included energy metabolism/mitochondrial-related (21%), protein synthesis and modification (14%), lipid metabolism (13%), and muscle-related (6%) transcripts. Together, the predominant pattern reflected an energetic shift toward fatty acid beta-oxidation and integrated alterations in both myofibers and supportive tissues. The response of monkey rectus muscles to monocular deprivation was considerably less severe. CONCLUSIONS: The visual deprivation paradigms used in this study mimic alterations that are associated with the common disorders of strabismus, congenital cataract, and amblyopia. These data show that postnatal EOM maturation is broadly susceptible to changes in activity patterns that are a consequence of visuomotor maldevelopment. The data extend the concept of an EOM-critical period and establish that activity patterns in developing eye movement systems play vital determinant roles in the novel EOM phenotype.

Animals↗
PubMed1976

A "critical period" for cervically-stimulated prolactin relase.

To investigate the role of ovarian steroids in the initiation and maintenance of the prolactin surges typical of pseudopregnancy in the rat, the pattern of plasma prolactin concentrations resulting from cervical stimulation of long-term ovariectomized rats was determined. Cervical stimulation of rats, ovariectomized 2-4 weeks previously, at 1900 h (lights on 0600-1800 h) resulted in a surge of prolactin which was initiated 4-6 h later and which was similar in timing and duration to the nocturnal prolactin surge of intact, pseudopregnant rats. Daily prolactin surges continued for 6 days but declined thereafter. Because plasma progesterone levels were elevated significantly after cervical stimulation, the experiment was repeated iin adrenalectomized-ovariectomized rats. Prolactin surges were still observed, demonstrating that ovarian and adrenal steroids are required neither for initiation nor maintenance of prolactin surges after cervical stimulation. Cervical stimulation at different times of the day (1900 h, 2400 h or 0400 h) always resulted in a surge of prolactin which peaked at 0300-0700 h. The latency from cervical stimulation in the peak of the prolactin surge was 8 h for the 1900 h group, 5 h for the 2400 h group, and 3 h for the 0400 h group. Thus, the appearance of prolactin surges is related to the time of day rather than to the time cervical stimulation is applied, demonstrating the existence of a "critical period" for cervically-induced prolactin release.

Adrenalectomy↗
PubMed1994

Identification of cDNA clones expressed selectively during the critical period for visual cortex development by subtractive hybridization.

We have used the method of subtractive hybridization to isolate cDNA clones of mRNAs expressed in abundance in the visual cortex of 30-day-old kittens but absent or in lower abundance in the adult cat visual cortex. Of 12,000 colonies screened, 200 clones which hybridized to the subtracted probe were isolated and characterized. Northern blots confirmed the specificity of the vast majority of the isolated clones. 120 of the 200 clones were sequenced and the EMBL and GenBank (release 76) database were searched for known identities using FASTA and BLAST programs. Twenty-seven of these sequenced clones were identifiable. The identities showed that these sequences code for proteins involved in a variety of cellular processes. These include cell-cell interaction (TAPA-1, contactin, tachykinin receptor, phospholipase A2), cellular remodeling (C1q beta isoform, heat shock protein), neurofilament assembly (alpha tubulin and alpha internexin), neurotransmitter release (VAMP-2, amphiphysin, carboxypeptidase E, scg 10 and proton channel), energy metabolism (mitochondrial hinge protein, ADP/ATP transporter, cytochrome oxidase subunits), RNA processing (helix destabilizing protein, ribonucleoprotein) and protein synthesis (eIF-4A initiation factor, ribosomal protein S27). The results show that gene expression in the kitten visual cortex differs rather little from that of the adult visual cortex since over 98% of the sequences appear common. The relatively rare kitten-specific sequences are likely to form the basis for the critical period plasticity in this system.

Aging↗
PubMed2004

Children grow and horses race: is the adiposity rebound a critical period for later obesity?

BACKGROUND: The adiposity rebound is the second rise in body mass index that occurs between 3 and 7 years. An early age at adiposity rebound is known to be a risk factor for later obesity. The aim here is to clarify the connection between the age at rebound and the corresponding pattern of body mass index change, in centile terms, so as to better understand its ability to predict later fatness. DISCUSSION: Longitudinal changes in body mass index during adiposity rebound, measured both in original (kg/m2) and standard deviation (SD) score units, are studied in five hypothetical subjects. Two aspects of the body mass index curve, the body mass index centile and the rate of body mass index centile crossing, determine a child's age at rebound. A high centile and upward centile crossing are both associated separately with an early rebound, while a low centile and/or downward centile crossing correspond to a late rebound. Early adiposity rebound is a risk factor for later fatness because it identifies children whose body mass index centile is high and/or crossing upwards. Such children are likely to have a raised body mass index later in childhood and adulthood. This is an example of Peto's "horse racing effect". The association of centile crossing with later obesity is statistical not physiological, and it applies at all ages not just at rebound, so adiposity rebound cannot be considered a critical period for future obesity. Body mass index centile crossing is a more direct indicator of the underlying drive to fatness. SUMMARY: An early age at adiposity rebound predicts later fatness because it identifies children whose body mass index centile is high and/or crossing upwards. Such children are likely to have a raised body mass index later. Body mass index centile crossing is more direct than the timing of adiposity rebound for predicting later fatness.

Adipose Tissue↗
PubMed1986

Permanent alteration of peptide feedback on dopamine neurons after injection of alpha-melanotropin antiserum at a critical period of postnatal development.

Tonic inhibition of alpha-MSH secretion by the tubero-hypophyseal dopamine (DA) neurons of the rat starts at the end of the first postnatal week, after a peak in plasma MSH at days 5 and 6. In order to obtain information on the maturation of central control, we studied the development of alpha-MSH feedback on DA neurons and the possible role of circulating peptide. The characteristic response of these DA neurons to i.p. alpha-MSH, i.e., an acute rise in cellular fluorescence intensity as determined by microfluorimetry, was not yet detected at day 4 but present at day 8. When rats were injected i.v. with antiserum to alpha-MSH on days 5 and 6 and tested as adults, their DA neurons failed to react to i.p. alpha-MSH (2-100 micrograms/kg), but they were still responsive to prolactin (600 micrograms/kg). The DA system was already unresponsive to alpha-MSH at postnatal day 8. Antiserum injection on days 11 and 12, when plasma MSH is low, did not affect the reaction of DA neurons to alpha-MSH on day 14. These developmental processes were analogous in both sexes. Injections of control serum were ineffective. Our observations indicate that the feedback reaction of DA neurons to alpha-MSH develops in conjunction with the onset of inhibitory control of MSH release. The presence of alpha-MSH during a critical period appears to be necessary for the development of the responsiveness of DA neurons to the peptide hormone.

Aging↗
PubMed1998

There is a limited critical period for dopamine's effects on D1 receptor expression in the developing rat neostriatum.

Neonatal lesions of the dopamine (DA) system have different behavioral and neurochemical effects than lesions made in adulthood. Previous data from this laboratory have indicated that in the early postnatal period, lesions to the DA system induced by instrastriatal 6-hydroxydopamine (6-OHDA) result in a rapid and permanent loss of striatal D1 binding sites, but D2 receptor binding is unaffected. The length of the postnatal period within which neonatal instrastriatal 6-OHDA administration is effective in modulating D1 receptor binding is not known. To determine when D1 and D2 receptors are vulnerable to lesions of the DA system, we administered 6-OHDA intrastriatally to damage the DA innervation at different ages in the early postnatal period, at day of birth/postnatal day 1 (P0/1), P7 or P15 and examined DA receptor binding at P90 with quantitative autoradiography. Using [3H]mazindol binding to DA transporters (DAT) to verify the extent of the lesion, we then quantified the number of D1 binding sites using [3H]SCH23390 and D2 sites with [3H]spiroperidol. There were significant reductions in DAT sites at P0/1 (78 to 88%) and P7 (67 to 81%) but less significant changes at P15 (34 to 50% losses). The lesions were most effective for the dorsal caudate-putamen than more ventrally or in the nucleus accumbens. Our results demonstrate a significant reduction in D1 sites in all regions of the neostriatum following lesions at P0/1. The dorsal caudate-putamen was affected the most (51% loss, and the nucleus accumbens (41%) and ventral caudate-putamen less so (31%). No significant changes in D1 receptors were found at P7 or P15 and D2 receptors were unaffected with lesions in any of the age groups. The results indicate that there is a critical period for affecting expression of D1 receptors and this effect may, in addition, be related to the pattern of DA loss. Additionally, regulation of D2 receptors by this degree of loss of DA innervation does not occur during the first two weeks postnatally.

Aging↗
PubMed2006

Functional local connections with differential activity-dependence and critical periods surrounding the primary auditory cortex in rat cerebral slices.

Sensory information is processed in neural networks connecting the primary sensory cortices with surrounding higher areas. Here, we investigated the properties of local connections between the primary auditory cortex (area 41) and surrounding areas (areas 20, 36, 18a and 39) in rat cerebral slices. Neural activities elicited by repetitive electrical stimulation were visualized using the activity-dependent changes in endogenous fluorescence derived from mitochondrial flavoproteins, which mostly reflect activities produced by polysynaptic glutamatergic transmission. Polysynaptic feedforward propagation was dominant compared with the corresponding polysynaptic feedback propagation between the primary (area 41) and secondary (areas 20 and 36) auditory cortices, while such a tendency was less clear in other pathways. Long inter-areal (>1 mm) propagation with the same dominancy was observed after layer V stimulation between areas 41 and 20, and was not affected by cutting the underlying white matter. Activity-dependent changes in neural activities induced by low-frequency stimulation in the presence of 1 microM bicuculline were investigated using Ca2+ imaging. Significant potentiation of the polysynaptic Ca2+ activities was only observed in polysynaptic feedforward pathways from the primary to secondary auditory cortices. Experience-dependence of the connections between areas 41 and 20 was investigated using flavoprotein fluorescence imaging. The activities from areas 41 to 20 were reduced by cochlear lesions produced at P12 but not at P28, while the activities from areas 20 to 41 were reduced by the lesions at P28, suggesting the critical period for the polysynaptic feedforward connection was before P28, while for the polysynaptic feedback connection was after P28.

Animals↗
PubMed1991

The critical period for mullerian duct regression in the dog embryo.

The embryonic period during which Mullerian duct regression and Mullerian Inhibiting Substance (MIS) secretion occur was determined in canine embryos removed from timed pregnancies (32, 36, 37, 39, 42, and 46 days gestation). Sex chromosomes of each embryo were identified in metaphase spreads prepared from fibroblast cultures. Testicular differentiation, defined by seminiferous tubule formation and the presence of Sertoli cells and Leydig cells, and the degree of Mullerian duct regression were determined by careful morphologic analysis of histologic sections of canine embryonic gonads (n = 20) and Mullerian ducts (n = 20). MIS was detected immunohistochemically in embryonic testes using avidin-biotin complex enhancement of a specific rabbit polyclonal anti-MIS antibody. Testicular differentiation was observed at 36 days gestation. The earliest evidence of Mullerian duct regression in male embryos was observed at 36 days gestation, and regression was completed by 46 days gestation. Positive staining for MIS was present in testes from 36 to 46 days (n = 9). Staining was absent in the undifferentiated testis (n = 1) at 32 days gestation and in ovaries at all ages tested (n = 10). Thus, MIS is normally present throughout the critical period for Mullerian duct regression in the embryonic male dog.

Animals↗
PubMed2004

Ontogeny of glucocorticoid receptor and 11beta-hydroxysteroid dehydrogenase type-1 gene expression identifies potential critical periods of glucocorticoid susceptibility during development.

Glucocorticoids play important roles in organ development and 'fetal programming'. Fetal exposure to excess glucocorticoids reduces birth weight and causes later hypertension. To investigate these processes further we have determined the detailed ontogeny in the mouse of the glucocorticoid receptor (GR) and 11beta-hydroxysteroid dehydrogenase type-1 (11beta-HSD1), which amplifies glucocorticoid levels locally; the ontogeny was determined using in situ hybridisation from embryonic day 9.5 (E9.5, term=E19) until after birth. At E9.5 fetal GR mRNA levels are very low, except in fetal placenta. GR gene expression rises during gestation with striking tissue-specific differences in timing and extent. Before E13.5, an increase is clear in gastrointestinal (GI) and upper respiratory tracts, discrete central nervous system (CNS) regions, precartilage and especially in the liver (E10.5-E12). Later, further increases occur in lung, GI and upper respiratory tracts, muscle, pituitary and thymus. In a few tissues such increases are temporary, e.g. ureteric ducts (E13.5-E16.5) and pancreas (E14.5-E16.5, expression later falling sharply). Fetal 11beta-HSD1 mRNA expression is first clearly observed at E14.5-E15, initially in the fetal placenta then in the umbilical cord. Later, 11beta-HSD1 expression is seen as follows: (i) from E15 in lung and liver, rising strongly; (ii) thymus, from E15 (lower level); (iii) at low levels in a few brain regions, including the hippocampus (E16.5+); and (iv) in muscle group fascial planes and tendon insertions. This is the first detailed study of the ontogeny of these two genes and, in combination with previous work on the ontogeny of 11beta-HSD2 and the mineralocorticoid receptor, suggests potential critical periods of glucocorticoid sensitivity during development for several organ systems.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed2003

Requirement of a critical period of GABAergic receptor blockade for induction of a cAMP-mediated long-term depression at CA3-CA1 synapses.

Previous reports show that bath application of the adenosine 3' : 5'-cyclic monophosphate (cAMP) analog, Sp-cAMPS, induces a protein kinase A (PKA)-dependent and protein synthesis-dependent long-term potentiation (LTP) at hippocampal CA3-CA1 synapses. Recently, we reported a novel form of long-term depression (LTD) induced by concurrent application of Sp-cAMPS and picrotoxin, the gamma-aminobutyric acid type A (GABA(A)) receptor antagonist. In the present study, we further investigated the mechanisms underlying such cAMP-mediated LTD. Synaptically connected CA3 and CA1 cells of hippocampal slice cultures were impaled by sharp electrodes. Excitatory postsynaptic potentials recorded from a CA1 pyramidal cell were evoked by single action potentials in a CA3 cell. Picrotoxin was applied to slices at various time points after Sp-cAMPS was perfused. We found that Sp-cAMPS-induced potentiation could be converted to depression when picrotoxin was applied within 30 min after perfusion of Sp-cAMPS. Picrotoxin applied 1 h after perfusion of Sp-cAMPS had no effect on Sp-cAMPS-induced synaptic potentiation. Once LTP was induced by Sp-cAMPS and expressed for 1 h, the subsequent application of Sp-cAMPS and picrotoxin produced no new changes in synaptic strength. Also, once LTD was induced and expressed for 1 h, subsequent Sp-cAMPS produced no new changes in synaptic strength. These findings suggest that a synapse is committed irreversibly to cAMP-mediated LTP or LTD during a critical period and that later signals cannot interconvert these two fates.

Animals↗
PubMed1983

A critical period in the onset of parturition in rats and uterine sensitivity to estradiol and progesterone.

The purpose of this paper was to impair normal parturition in rats in order to measure tissue levels of progestins and estrogens and compare these results with those of normal parturition in rats. Abnormal parturition was obtained by injection of isotonic saline into the uterine lumen of pregnant rats at the end of pregnancy or by handling the uterus. After each of these treatments on day 21 of pregnancy, parturition was impaired in 70 to 98% of the rats. When the treatments were carried out earlier or later in pregnancy, there was little or no impairment. Our results indicate transient discrepancies in plasma and tissue levels of steroids 6 h after treatment on day 21: 20 alpha-HP concentrations increased in treated rats compared to controls (uteri: 470%; p less than 0.01; ovaries: 89%; p less than 0.001); concomitantly, there was a sharp rise in P concentrations in uteri (+ 74% : p less than 0.05) and ovaries (+ 52%; p less than 0.05). Inversely, uterine concentrations of E2 decreased 6 h after treatment compared to controls (- 30%; p less than 0.05), although there was a transient rise of E2 in the ovaries (+ 30%; p less than 0.05). Twenty-four hours later, E2 concentrations were always lower in the uteri (- 30%; p less than 0.01). No change in E2 levels was noted in the uteri or ovaries of either the control or treated rats. The physiological significance of these changes and their consequences on uterine reactivity at term have been discussed. The data demonstrate that day 21 was a critical period in the parturient activity of the rat uterus which appears to be primarily affected by uterine levels of E2 between days 21 and 22 of pregnancy.

20-alpha-Dihydroprogesterone↗
PubMed2002

n-3 Deficient and docosahexaenoic acid-enriched diets during critical periods of the developing prenatal rat brain.

The last period of the intrauterine life in the rat (embryonic day 17 to 21, ED17-ED21) is demarcated by an increase in brain and body weight and active neuronogenesis. During this period, a rapid accumulation of DHA (22:6 n-3), unparalleled to other fatty acids, takes place. The details of DHA rapid acquisition in the fetal brain were investigated after imposing a diet deficient in n-3 fatty acids (FA) as of ED1 and subsequently examining the distribution of DHA in major brain phospholipid (PL) classes on ED20, having added on ED15 a triglyceride (TG) mixture enriched up to 43% with DHA. The n-3 deficiency maintained for 19 days resulted at ED20 in more than 30% reduction of DHA in PL, which was counterbalanced by an increase of docosapentaenoic acid (DPA, 22:5 n-6). No effect on body weight, nor major changes in PL composition or other FA in fetal brain PL were observed. Feeding dams a DHA-TG diet on ED15 induced an immediate increase of DHA in maternal liver PL, followed by a subsequent increase of DHA in fetal liver PL, as well as in fetal brain PL. Thus the content of fetal brain DHA in n-3 deficient embryos could be restored within 48 hours. Dietary manipulation of fetal tissues is a rapid phenomenon and can be used to enrich DHA at critical periods of development in utero.

Animals↗
PubMed1983

Maturation of monoamine neurotransmitters and receptors in cat occipital cortex during postnatal critical period.

The postnatal development of monoamine levels and receptors in the occipital cortex of the cat has been investigated using neurochemical techniques. The endogenous catecholamines (noradrenaline and dopamine) gradually increased with age, displaying an about 12-13-fold increase in their concentration from the newborn to the adult stage. 3H-dihydroalprendol (beta-adrenoceptor ligand) binding showed a rapid increase from the low value (25% of the adult value) at birth, peaking at the age of 7-9 weeks with a value of about 150% of adults. The beta-adrenoceptor binding stayed relatively constant at adult value from the age of 11 weeks throughout. Endogenous 5-hydroxytryptamine levels were at birth about 20% of the adult value and thereafter rapidly increased, peaking at the age of 3-5 weeks when it reached the adult value. Between the age of 7-13 weeks the 5-hydroxytryptamine level was about 50-60% of adult. The developmental pattern for 3H-5-hydroxytryptamine binding was similar to that of endogenous 5-hydroxytryptamine, although with certain quantitative differences. The 3H-5-hydroxytryptamine receptor binding showed a steep peak at an age of about 4 weeks when the binding was about 300% of the adult value. Thereafter the binding gradually levelled off in adulthood. Similar results were obtained in the frontal cortex, except for some quantitative differences. The present results thus indicate that both noradrenaline and 5-hydroxytryptamine nerve terminals develop, largely independent of their postsynaptic receptors, probably due to different developmental programs regulating their expression. The development of monoamine receptors appear to precede that of their nerve terminals. The different roles played by beta-adrenoceptors and 5-hydroxytryptamine receptors for the maturation of occipital cortex during postnatal critical period were discussed.

Animals↗
PubMed1994

A critical period for glutamate receptor-mediated induction of precocious puberty in female rats.

The excitatory amino acid glutamate and especially its NMDA subtype receptor are important components of the neural system that regulates sexual maturation. It is known that multiple daily injections of immature rats and monkeys with NMDA will induce precocious puberty. We have previously reported that a single daily injection of NMDA administered from 27 days of age to the day of vaginal opening (VO) is sufficient to synchronize and slightly accelerate (1-2 days) first ovulation in female rats. We have now optimized this treatment schedule and show that a higher dose of NMDA (20 mg/kg), or the racemic mixture N-methyl-D,L-aspartate (NMA; 30 mg/kg), initiated earlier in development (24 days to VO) significantly advances first ovulation (4 days). Rats induced to ovulate prematurely had normal estrous cycles. We also report that the same degree of precocity can be obtained when injections are discontinued well before first ovulation occurs. For example, NMA administered from day 21 to 25 or from day 24 to 28 accelerates sexual maturation to the same degree as if injections were continued until VO was observed. It is clear that the hypothalamic-pituitary-ovarian (H-P-O) axis is stimulated by daily NMDA treatment as shown by the dose-related luteinizing hormone (LH) release and by an estrogen-dependent rise in uterine weight. However, stimulation of the P-O axis with daily injections of GnRH (5 ng/100 g), which elicits an LH response slightly greater than NMDA (20 mg/kg), does not advance puberty. This suggests that NMDA induces some change in hypothalamic control which is not directly related to LH secretion. Interestingly, there also seems to be a critical period of NMDA effectiveness because daily injections of NMA (30 mg/kg) from day 16 to 20 do not induce precocious puberty. Since the ovaries respond with increased estrogen production (increased uterine weight) to gonadotrophin stimulation at this early age (16 days) we conclude that the hypothalamus may be relatively unresponsive to stimulation with NMDA. Paradoxically the hypothalamus is also hyporesponsive to NMDA in the period preceding spontaneous first ovulation. We now show that an LH dose-response curve for NMDA at age 28 days demonstrates that in NMDA-treated rats the LH response to NMDA is less than in the control group. Further, the hyporesponsiveness is not due to pituitary desensitization since an LH dose-response curve for GnRH at age 28 days is identical in the NMDA-treated and control groups.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2005

Adverse effects of prenatal exposure to atrazine during a critical period of mammary gland growth.

Prenatal exposure to 100 mg/kg atrazine (ATR) delays mammary gland (MG) development in resulting female offspring of Long-Evans rats. To determine if the fetal MG was sensitive to ATR effects during specific periods of development, timed-pregnant dams (n = 8/group/block) were dosed for 3- or 7-gestation day (GD) intervals (GD 13-15, 15-17, 17-19, or 13-19) with 100 mg ATR/kg/day or vehicle (C), and their offspring were evaluated for changes. Mammary glands taken from pups prenatally exposed to ATR displayed significant delays in epithelial development as early as postnatal day (PND) 4 compared to C, with continued developmental delays at later time points that varied by time of exposure. However, the most persistent and severe delays were seen in the GD 17-19 and GD 13-19 ATR exposure groups, demonstrating statistically similar growth retardation. Because MG developmental deficits persisted into adulthood, we hypothesized that ATR-exposed animals may have had difficulties nursing their young. Females exposed prenatally to either ATR (as defined) or C (n = 4 litters/group) were bred, and the resulting F(2) offspring from GD 17-19 and GD 13-19 exposure groups were significantly smaller in body weight (BW) than C. In a separate study, it was determined that ATR (25-100 mg/kg), delivered from GD 15-19, did not decrease fetal body weights on GD 20, even though the higher doses significantly decreased weight gain of the dosed dams. These data suggest that the consequences of brief ATR exposure during a critical period of fetal MG development (GD 17-19), are both delayed MG development of the offspring and inadequate nutritional support of F2 offspring, resulting in adverse effects on pup weight gain.

Animals↗