In several species, including humans, circulating insulin-like growth factor I (IGF-I) levels increase during the onset of puberty, suggesting that this peptide contributes to attaining sexual maturity. Because IGF-I elicits LHRH release from the median eminence (ME) of immature female rats in vitro, we hypothesized that it may represent one of the peripheral signals suspected to link somatic development to the LHRH-releasing system at puberty. We now present evidence in support of this concept. Quantitation of IGF-I messenger RNA (mRNA) levels by ribonuclease protection assay revealed that expression of the IGF-I gene did not change in the medial basal hypothalamus or preoptic area of female rats during peripubertal development. In contrast, the contents of both IGF-Ia and IGF-Ib mRNA, the two alternatively spliced forms of the IGF-I gene, increased significantly in the liver during the early proestrous phase of puberty. This change was followed by an elevation in serum IGF-I levels during the late proestrous phase of puberty along with a concomitant increase is serum gonadotropin levels. The proestrous change in serum IGF-I levels was accompanied by a selective increase in IGF-I receptor (IGF-IR) mRNA in the ME. Small doses of IGF-I (2-200 ng), administered intraventricularly, effectively induced LH release in both juvenile and peripubertal female rats, an increase prevented by prior immunoneutralization of LHRH actions. Importantly, intraventricular injections of IGF-I (20 ng), administered twice daily in the afternoon to immature animals, significantly advanced puberty. Thus, these results suggest that IGF-I of peripheral origin contributes to the initiation of female puberty by stimulating LHRH release from the hypothalamus, an effect that appears to be amplified by the increased synthesis of IGF-I receptors in the ME during first proestrus.

Objective To assess the impact of the newborn health component of a large-scale community-based integrated nutrition and health programme. Methods Using a quasi-experimental design, we evaluated a programme facilitated by a nongovernmental organization that was implemented by the Indian government within existing infrastructure in two rural districts of Uttar Pradesh, northern India. Mothers who had given birth in the 2 years preceding the surveys were interviewed during the baseline (n = 14 952) and endline (n = 13 826) surveys. The primary outcome measure was reduction of neonatal mortality. Findings In the intervention district, the frequency of home visits by community-based workers increased during both antenatal (from 16% to 56%) and postnatal (from 3% to 39%) periods, as did frequency of maternal and newborn care practices. In the comparison district, no improvement in home visits was observed and the only notable behaviour change was that women had saved money for emergency medical treatment. Neonatal mortality rates remained unchanged in both districts when only an antenatal visit was received. However, neonates who received a postnatal home visit within 28 days of birth had 34% lower neonatal mortality (35.7 deaths per 1000 live births, 95% confidence interval, CI: 29.2-42.1) than those who received no postnatal visit (53.8 deaths per 1000 live births, 95% CI: 48.9-58.8), after adjusting for sociodemographic variables. Three-quarters of the mortality reduction was seen in those who were visited within the first 3 days after birth. The effect on mortality remained statistically significant when excluding babies who died on the day of birth. Conclusion The limited programme coverage did not enable an effect on neonatal mortality to be observed at the population level. A reduction in neonatal mortality rates in those receiving postnatal home visits shows potential for the programme to have an effect on neonatal deaths.

KiSS-1 gene expression has been shown to increase as puberty approaches, and its peptide products, kisspeptins, are involved in LHRH secretion at puberty. Factors contributing to increased KiSS-1 expression, however, have not been identified; thus, the purpose of this study was to assess whether IGF-I could induce transcription of this gene in prepubertal female rats. IGF-I or saline was centrally administered to immature rats that were killed 2, 4, and 6 h later. Real-time PCR revealed that IGF-I induced (P < 0.01) KiSS-1 gene expression at 6 h in a tissue fragment that contained both the anteroventral periventricular (AVPV) and arcuate (ARC) nuclei. Subsequently, the AVPV and ARC nuclei were separated to assess whether region-specific effects could be identified. IGF-I stimulated (P < 0.01) KiSS-1 gene expression in the AVPV nucleus at 6 h after injection, with no change observed in the ARC nucleus. Serum estradiol (E2) levels were not altered at any time point after IGF-I, demonstrating that the increased KiSS-1 expression observed was not caused by an elevation in E2. Additionally, the IGF-I action to induce KiSS-1 gene expression in the AVPV nucleus was further demonstrated when the IGF-I was administered systemically. E2 appears to play an important permissive role because 1-d ovariectomized rats responded to IGF-I with increased (P < 0.01) KiSS-1 expression, whereas, 20 d after ovariectomy, when the E2 levels had fallen below assay sensitivity, the IGF-I was unable to induce KiSS-1 expression. The IGF-I effect was further demonstrated by showing that the IGF-I receptor antagonist, JB-1, blocked the IGF-I-induced increase in KiSS-1 expression. Collectively, these data indicate that IGF-I is an activator of the KiSS-1 gene in the prepubertal female rat.

CHWs' knowledge is one of the crucial aspects of health systems to improve the coverage of community-based newborn health care programmes as well as adherence to essential newborn care practices at the household level.

No abstract