Alternate-day fasting delays pubertal development in normal-weight mice but prevents high-fat diet-induced obesity and precocious puberty.

BACKGROUND/OBJECTIVES: Childhood obesity, particularly in girls, is linked to early puberty onset, heightening risks for adult-onset diseases. Addressing childhood obesity and precocious puberty is vital to mitigate societal burdens. Despite existing costly and invasive medical interventions, introducing lifestyle-based alternatives is essential. Our study investigates alternate-day fasting's (ADF) impact on pubertal development in normal-weight and high-fat diet (HFD)-induced obese female mice. METHODS: Four groups of female mice were utilized, with dams initially fed control chow during and before pregnancy. Post-parturition, two groups continued on control chow, while two switched to an HFD. Offspring diets mirrored maternal exposure. One control and one HFD group were subjected to ADF. Morphometry and hormone analyses at various time points were performed. RESULTS: Our findings demonstrate that ADF in normal-weight mice led to reduced body length, weight, uterine, and ovarian weights, accompanied by delayed puberty and lower levels of sex hormones and growth hormone (GH). Remarkably, GH treatment effectively prevented ADF-induced growth reduction but did not prevent delayed puberty. Conversely, an HFD increased body length, induced obesity and precocious puberty, and altered sex hormones and leptin levels, which were counteracted by ADF regimen. Our data indicate ADF's potential in managing childhood obesity and precocious puberty. CONCLUSIONS: ADF reduced GH and sex hormone levels, contributing to reduced growth and delayed puberty, respectively. Therefore, parents of normal-weight children should be cautious about prolonged overnight fasting. ADF prevented HFD-induced obesity and precocious puberty, offering an alternative to medical approaches; nevertheless, further studies are needed for translation into clinical practice.

The Use of Morning Urinary Gonadotropins and Sex Hormones in the Management of Early Puberty in Chinese Girls.

CONTEXT: Although gonadotropin-releasing hormone stimulation test (GnRHST) is the gold standard in diagnosing central precocious puberty (CPP), it is invasive, expensive, and time-consuming, requiring multiple blood samples to measure gonadotropin levels. OBJECTIVE: We evaluated whether urinary hormones could be potential biomarkers for prepuberty or postpuberty, aiming to simplify the current diagnosis and prognosis procedure. METHODS: We performed a cross-sectional study of a total of 355 girls with CPP in National Clinical Research Center for Child Health in China, including 258 girls with positive and 97 girls with negative results from GnRHST. Twenty patients received GnRH analogue (GnRHa) treatment and completed a 6-month follow up. We measured luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, prolactin, progesterone, testosterone, and human chorionic gonadotropin in the first morning voided urine samples. RESULTS: Their urinary LH levels and the ratios of LH to FSH increased significantly with the advancement in Tanner stages. uLH levels were positively associated with basal and peak LH levels in the serum after GnRH stimulation. A cutoff value of 1.74 IU/L for uLH reached a sensitivity of 69.4% and a specificity of 75.3% in predicting a positive GnRHST result. For the combined threshold (uLH ≥ 1.74 + uLH-to-uFSH ratio > 0.4), the specificity reached 86.6%. After 3 months of GnRHa therapy, the uLH and uFSH levels decreased accordingly. CONCLUSION: uLH could be a reliable biomarker for initial CPP diagnosis and screening; uLH could also be an effective marker for evaluating the efficacy of clinical treatment.

The incidence of brain lesions in central precocious puberty: The main cause for Chinese boys was idiopathic.

OBJECTIVE: Many studies show that brain lesions are the main cause of central precocious puberty (CPP) in males. However, the association rate has not been reported in China. This study aimed to assess the frequency of both abnormal and likely pathologic brain lesions by magnetic resonance imaging (MRI) in Chinese boys with CPP. DESIGN: This is a retrospective cross-sectional single-centre study. PATIENTS: 396 CPP boys were recruited from 2011 to 2019 in Children's Hospital, Zhejiang University School of Medicine, and 129 were eligible for our study. MEASUREMENTS: Diagnosis age, bone age, weight (kg), height (cm), puberty stage, MRI results and levels of sexual hormone were analysed. RESULTS: The number of CPP boys is increasing from 2011 to 2019 in China. Brain MRI findings were normal in 83.7% of CPP boys. Only 21 (16.3%) CPP boys were found with abnormal MRI findings including hamartoma, pineal cyst and other minor changes. CONCLUSION: In China, there is an increasing trend of male CPP over the last decade and the main cause is idiopathic, rather than pathogenic brain lesions. Further investigations about the aetiology for CPP with pathological brain lesions are needed.

Ethnic-specific genetic association of variants in the corticotropin-releasing hormone receptor 1 gene with nicotine dependence.

Twin and family studies indicate that smoking addiction is highly influenced by genetic factors. Variants in the corticotropin-releasing hormone receptor 1 (CRHR1) gene have been associated with alcoholism and depression. In this study, we tested five single nucleotide polymorphisms (SNPs) in CRHR1 for their association with ND, which was assessed by smoking quantity (SQ), the Heaviness of Smoking Index (HSI), and the Fagerström test for ND (FTND) in 2,037 subjects from 602 families of either European American (EA) or African American (AA) ancestry. Association analysis of the five SNPs revealed a significant association of rs171440 with SQ in the AA sample and with SQ and FTND in the pooled AA and EA samples. Haplotype-based association analysis indicated significant association of haplotypes C-C (56.9%) and T-C (38.9%), formed by SNPs rs171440 and rs1396862, with SQ in the AA sample, C-C-G (47.6%) with SQ, and T-C-G (42.3%), formed by SNPs rs171440, rs1396862, and rs878886, with SQ and FTND in the pooled AA and EA samples. However, none of these associations remained significant after correction for multiple testing. Together, our results provide suggestive evidence for the involvement of CRHR1 in ND, which warrants further investigation using larger independent samples.