Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0029713 (immaturity)
 4,335 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leprechaunism is a rare genetic disorder characterized by physical abnormalities, intrauterine and postnatal growth retardation, poorly developed subcutaneous fat and muscle at birth, and early death. This patient, who was a 1.5 year-old female with typical clinical features of leprechaunism, had relatively high levels of plasma GH and IGF-I/SMC but no glucose intolerance or insulin resistance. Studies were undertaken to elucidate (1) the differences among some kinds of methods for IGF-I/SMC measurement, (2) the distribution patterns of IGF-I/SMC between two kinds of its binding protein (SMBP) in plasma, and (3) the dynamics of IGF-I/SMC receptor in her erythrocytes and liver microsomal membranes. The results were as follows: (1) The level of IGF-I/SMC measured by Nichols radioimmunoassay kit was 1.33U/ml, which was higher than that of infants the same age. Conversely, it was lower than that of the control which was measured by radioimmunoassay using recombinant IGF-I/SMC after acid-ethanol or Seppak C18 extraction. (2) By Sephadex G150 gel-chromatography, immunoreactive IGF-I/SMC was eluted predominantly in 150K region, and two apparent peaks of unsaturated somatomedin binding protein (USBP) were determined in a neonatal infant (appropriate to date), a normal adult and an infant of the same age as this patient. On the other hand, immunoreactive IGF-I/SMC was located only in the fractions corresponding to 40K region, and only one peak of USBP could be estimated in the region of 40K dalton. (3) The IGF-I/SMC receptor in the patient's erythrocytes possessed significantly lower binding affinity but higher binding capacity in comparison with that of the normal neonate and adult. In addition, the receptor in liver microsomal membranes obtained from this patient at autopsy also indicated lower affinity but higher capacity than that of fetuses at more than 19 weeks of gestation. This was coincident to that of fetuses less than 19 weeks of gestation. These results suggested that this patient resembled the intrauterine fetus before midgestation not only in the co-relationship among GH, IGF-I/SMC and its binding proteins, but also in the characteristics of its receptor. The severe growth retardation existing in this patient may be, at least partly, due to the abnormality and/or immaturity of IGF-I/SMC function. It is speculated that leprechaunism could be classified in relation to fetal growth mechanism by aspects of biological functions of IGF-I/SMC during development.
 ...
PMID:[A case of leprechaunism with disorders of insulin-like growth factor-I(IGF-I)/somatomedin C(SMC) binding protein and its receptor]. 247 74

Studies of the maturation of hypothalamic control of adenohypophyseal hormone secretion are reviewed with particular reference to the somato-tropic axis in the ovine fetus. In the ovine fetus, circulating growth hormone concentrations are 20-fold higher than postnatal concentrations falling in the 72 h prior to delivery. These high fetal growth hormone concentrations are postulated to reflect an immaturity of hypothalamic control mechanisms. Synthetic human growth hormone releasing factor (10 micrograms/kg) markedly stimulates fetal circulating growth hormone release between 77 and 135 days of gestation. The response decreases with advancing maturation. Thus fetal growth hormone release is not under maximal stimulation. Fetal growth hormone, thyrotropin and gonadotropin release is pulsatile in nature and the growth hormone and thyrotropin pulses have exaggerated amplitudes compared to the postnatal pattern. It is suggested that in each case, this enhanced pulsatility is a consequence of immature feedback loops. Stereotaxic lesioning of the fetal median eminence at 110 days of gestation abolishes the pulsatility of fetal growth hormone release. However the basal secretion of growth release remains elevated in some fetuses compared to postnatal growth hormone concentrations. The basis for this high basal rate of secretion is speculative but it is postulated to reflect immaturity of inhibitory control mechanisms, in particular of the negative feedback loop. Neuropharmacological studies of circulating growth hormone release in the perinatal period are reviewed. These demonstrate that the potential for many neurotransmitters to influence fetal circulating growth hormone release has differentiated by midgestation. However antagonist studies have not demonstrated a tonic role for any stimulatory neurotransmitters, only for the inhibitory neurotransmitter, GABA. Growth hormone does not exert a major influence upon fetal growth. Studies of the ontogeny of growth hormone receptors in the ovine liver show that somatotropic receptors are first detected in the newborn lamb suggesting receptor immaturity as the basis for this lack of an effect of growth hormone in utero. The two insulin-like growth factors, IGF-I and IGF-II show different patterns of secretion in the perinatal period. IGF-I levels are low in utero, rise gradually through gestation with a marked postnatal rise perhaps related to the development of hepatic growth hormone receptors. IGF-II levels are high in the fetus and fall over the 3 days prior to delivery but are not affected by fetal decapitation. The role of placental lactogen as a stimulus of fetal IGF-II secretion is suggested.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Functional maturation of the neuroendocrine system in the perinatal period: studies of the somatotropic axis in the ovine fetus. 674 30

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.
 ...
PMID:Evidence that neuropeptide Y could represent a neuroendocrine inhibitor of sexual maturation in unfavorable metabolic conditions in the rat. 840 31

There is increasing evidence to suggest that insulin-like growth factors (IGF) I and II play a crucial role in fetal lung development. Expression of IGF-I and II has been demonstrated to be predominant during fetal life and decreases prior to birth. Antenatal glucocorticoids are reported to improve lung immaturity. The aim of this study was to investigate the effect of antenatal glucocorticoid administration on IGF-I and II expression in nitrofen-induced congenital diaphragmatic hernia (CDH) in rats. A CDH model was induced in pregnant rats following administration of 100 mg nitrofen on day 9.5 of gestation (term = 22 days). Dexamethasone (0.25 mg/kg) was given intraperitoneally on days 18.5 and 19.5 of gestation. Cesarean section was performed on day 21. The fetuses were divided into three groups: I, normal controls; II, nitrofen-induced CDH; and III, nitrogen-induced CDH with antenatal dexamethasone treatment. mRNA was extracted from whole lung and a reverse transcription-polymerase chain reaction (RT-PCR) was performed to evaluate the relative amounts of IGF I and II mRNA. Levels of mRNA were expressed as a ratio of the band density divided by that of beta-actin, a housekeeping gene known to be expressed at a constant level. Immunohistochemistry using anti-rat IGF I and II antibody was also performed in each group. Levels of IGF I mRNA were significantly increased in group II (0.50 +/- 0.08) compared to group I (0.34 +/- 0.10) or group III (0.32 +/- 0.06) (P < 0.05). Levels of IGF II mRNA were also significantly increased in group II (0.95 +/- 0.20) compared to group I (0.42 +/- 0.07) or group III (0. 31 +/- 0.09) (P < 0.05). Strong IGF I and II expression was observed in the hypoplastic CDH lung (group II), mainly in the bronchiolar epithelium. IGF I and II expression in group I and III lungs was either absent or weak. The finding of significant reductions in IGF I and II mRNA and protein levels in dexamethasone-treated CDH lung suggest that dexamethasone may accelerate the fetal stage of lung development.
 ...
PMID:Effect of antenatal glucocorticoid administration on insulin-like growth factor I and II levels in hypoplastic lung in nitrofen-induced congenital diaphragmatic hernia in rats. 1037 16