The development of puberty is associated with the initiation of HPG axis function. Various environmental factors, such as contamination of food and water by environmental endocrine disruptors and estrogen; lifestyle changes; intercountry adoption of children and increased obesity due to overnutrition, etc., all contribute to the onset of precocious puberty through their effects on the HPG axis or even through their effects on genes. The early onset of breast development, but not the early onset of menstruation, i.e., the extended time between breast development and menarche, suggests that breast development is due to the influence of exogenous estrogen rather than the initiation of the HPG axis. This further indicates the important role of environmental factors in promoting the increased incidence of precocious puberty. 1, Kisspeptin and its receptor GPR54 Kiss-1 is a gene associated with puberty initiation. the product encoded by Kiss-1, Kisspeptin, binds to its receptor GPR54 and stimulates GnRH-dependent LH and FSH release mainly by acting on GnRH neurons. KISS-1 is a potent stimulator of GnRH secretion, and it can regulate the feedback of sex hormones in both directions at the hypothalamic level. Genetic studies have shown that its inactivating mutation leads to hypogonadotropic gonadal dysplasia and activating mutation leads to precocious puberty, and this effect may also be regulated by hypothalamic gonadotropin-releasing hormone. Studies in female rats with precocious puberty revealed that Kiss-1 expression in hypothalamic mRNA gradually increased during early and mid-late puberty in female rats with true precocious puberty, suggesting that Kiss-1 may be associated with the onset of true precocious puberty. Recent studies have identified a mutation in GPR54 in a female with precocious puberty, which resulted in the replacement of codon 386 arginine by proline. In vitro culture studies have shown that this mutation causes prolonged activation of the intracellular signaling pathway associated with the response, demonstrating that the mutation is associated with precocious puberty. Studies have shown that mutations in the LH receptor gene mainly cause familial precocious puberty in males and are autosomal dominant. Mutations in the LH receptor gene can lead to abnormal development of sex hormone target organs. Activating mutations in the LH receptor gene can lead to precocious puberty in family males. Activating mutations in the FSH receptor can increase FSH secretion and lead to sexual maturation. Male carriers of activating mutations exhibit testicular mesenchymal hyperplasia and gigantism, while female carriers exhibit precocious puberty, polycystic ovary syndrome, or premature menopause. In FSH receptor gene testing in girls with gonadotropin non-dependent precocious puberty, the A307T and S680D mutations were found in exon 10. ER is widely present in various animals and has a transcription factor role, which involves the expression and regulation of genes in female vertebrate tissues. It plays a key role in the development of secondary sexual characteristics and maintenance of the reproductive cycle in females, and affects fertility. The ER gene test conducted by Bing Li et al. in female patients with precocious puberty revealed the presence of the R548C mutation in exon 8, which was shown to be highly active in vitro by constructing plasmid vectors and expression, and presumably may also have corresponding activity in vivo, leading to precocious puberty in girls. 5. Neuroendocrine factors affecting GnRH neurons The mechanism of cyclic release of GnRH neurons is not well understood. It is hypothesized that there are neurons in the median hypothalamic bulge that issue synchronized and rhythmic neural impulses, and these neurons are called fluctuating generators. The inhibition of these generators needs to be mediated by factors that may include active amino acids, norepinephrine, dopamine, opioid-like peptides, etc. III. Environmental factors that increase the incidence of precocious puberty Changes in various environmental factors lead to an increased incidence of precocious puberty through their effects on the HPG axis and possibly through their effects on the relevant genes. The influence of environmental factors on pubertal development may be multifaceted. The advancement of breast development without a significant advancement of menarche, i.e., the prolonged time from breast development to menarche, suggests that breast development is due to the influence of exogenous estrogens rather than the initiation of the HPG axis. This further indicates that environmental factors are important. 1. Environmental endocrine disrupting compounds (EDCs), through their effects on the HPG axis and possibly on the related genes, have contributed to the increased incidence of precocious puberty. The “milk powdergate” incident has increased our attention to the influence of environmental factors on the endocrine system. The influence of environmental factors on pubertal development may be multifaceted. EDCs are substances present in the environment that can interfere with various parts of the endocrine system and cause abnormal effects; EDCs can affect the synthesis, secretion, and transport of natural hormones and bind to hormone receptors to produce estrogenic or anti-androgenic activity, which can alter the function of the endocrine system in humans and wild animals, leading to reproductive, developmental, and behavioral abnormalities. Studies have shown that mammary development is advanced without significant advancement in the timing of first menstruation. The prolonged time from mammary development to first menstruation suggests that mammary development and early appearance of pubic hair are due to the influence of exogenous estrogens rather than the HPG axis. Substances released into the environment by detergents, pesticides, insecticides and the plastics industry and their decomposition products can become EDCs in nature. these substances have some common characteristics in the environment chemically stable and can exist for a long time; most are highly lipid soluble and easily absorbed by the body, but not easily biodegraded and not easily excreted, and can accumulate through the food chain by enrichment in the ecosystem. EDCs can EDCs are mostly small molecules that can bind to estrogen receptors and can also act with natural estrogens to stimulate the production of estrogenic effects. EDCs can interfere with the differentiation of reproductive organs when exposed before birth, and can interfere with the development of the reproductive system when entering the body after birth, especially during puberty. Dibutyl phthalate (DBP) and 2-ethylhexyl phthalate are widely used plasticizers with estrogenic activity. A study showed that DBP and DEHP were detected in the serum of 27,3% and 22,7% of girls with precocious puberty, respectively, while only 4% and 3% of normal children had DBP and DEHP detected. early. Environmental estrogens include natural estrogens, synthetic estrogens and environmental pollutants. They differ greatly in structure and have many different ways of interfering with estrogen, but they all have the following four abilities: ① imitate endogenous hormones; ② antagonize endogenous hormones; ③ disrupt the production and metabolism of endogenous hormones; ④ disrupt the production and metabolism of hormone receptors. According to the FDA, the acceptable daily amount of estradiol through food is 0,43 ng/d for boys and 3,24 ng/d for girls, and the excessive intake of estradiol depends on the concentration of steroids in the meat. The concentration of steroids in cattle with and without steroids varies considerably. The highest concentration of estradiol is found in the tissues of pregnant heifers. If this pregnant beef is eaten, it is estimated that each 100 g of beef can result in an intake of 1600 ng of estradiol per day in children. This intake significantly exceeds FDA regulations. Hexenoestradiol is a synthetic hormone, and in 2006, 40 random samples of chicken sold in Nanyang City were tested for hexenoestradiol to varying degrees. This illustrates the seriousness of estrogen contamination in food. Therefore, estrogen contamination of food is one of the possible causes of premature maturity. Nowadays, melons and vegetables sold in the market are big and beautiful, but taste bland. These plant hormones are also called plant growth regulators. Shenyang City collected 2 supermarkets and 3 farmers’ markets to sell all kinds of fruit samples, ethylene glycol (plant ripening agent) detection rate of 92.00%. Domestic fruit 42, 38 detected, the detection rate of 90, 00%; imported fruit 8, the detection rate of 100, 00%. This shows the seriousness of estrogen contamination in food. In addition fungi and the toxins they produce such as zearalenol, not only contaminate corn, but also can contaminate barley, wheat, oats, sorghum and other grains. Contamination can occur before the grain is harvested or inappropriately stored after harvest. The toxin produced by the fungus in soil and its metabolites can also act on the estrogen receptor of the cell, which has a lower affinity to the estrogen receptor than endogenous estrogen; the fungal toxin can exert estrogenic and pro-proliferative effects after binding to the estrogen receptor; due to its estrogenic effects, it promotes the pulsatile secretion of the hypothalamic-pituitary-gonadal axis and triggers puberty. 3. Psychological/social factors A case-control study of 60 children with precocious puberty and 120 children without precocious puberty showed that factors such as parents frequently learning or consulting about parenting, frequent consumption of animal foods, frequent consumption of nutritional supplements, continuous use of adult chemical products, little time for extracurricular sports, and poor family relationships were correlated with precocious puberty in children. In 2006, a questionnaire survey of children with precocious puberty aged 6-9 years in Shenzhen showed that children in the precocious puberty group spent more time watching TV than the control group; the detection rate of precocious puberty was higher in children with family history of hypertension, diabetes and thyroid disease. This indicates that lifestyle has a relationship with the onset of precocious puberty, which can also be influenced by changes in psychological factors. a survey conducted in 2000 on girls in provincial capitals nationwide showed that girls in the northwest, where the economy and living standards are backward, had later menarche than girls in economically developed areas, indicating the influence of regional differences, living environment and economic development on pubertal development. The incidence of precocious puberty increases in children adopted intercountry after the age of 2. Changes in growth patterns after the age of 2 are likely to have certain endocrine effects that increase the risk of precocious puberty onset. Changes in dietary habits and growth patterns may contribute. Psychological factors also play a role: Indian children who immigrated between 3 and 6 years of age have a higher chance of developing precocious puberty than children adopted under 2 years of age. Early experiences with emotions and emotional communication can dramatically affect the development of the right brain hemisphere, especially the limbic system. This system, in turn, contributes to the control of changes in the vegetative response to emergency situations, and this stress response may affect hypothalamic pituitary function. It is inferred that intercountry adopted children experience more stressful life events and are more likely to develop precocious puberty than children who migrate with their parents. Older children are more likely to be affected by psychological stress factors, so children adopted after the age of 2 have a significantly higher risk of precocious puberty than children adopted at a younger age. 4. Dietary and nutritional factors: A questionnaire survey of children aged 6-9 with precocious puberty in Shenzhen in 2006 showed that children in the precocious puberty group were significantly more likely to consume beverages, meat and poultry, health supplements, and soup with Chinese herbs. The children in the precocious group were significantly higher than the normal children group. BMI is negatively correlated with the time of menarche. China’s Shenzhen 2004 survey showed that female precocious puberty is related to nutritional metabolism. This may be due to the increase in body fat caused by overnutrition and the increased secretion of leptin from adipocytes, which promotes the release of gonadotropins and leads to precocious puberty. The prevalence of precocious puberty was higher in intercountry adopted children than in children who immigrated with their families, suggesting that genetic factors do not explain these differences. The risk of precocious puberty was not significantly higher in children who migrated with their families because their dietary habits did not change and their growth pattern was relatively stable. The structure of the adopted children’s diet, as well as the change in the total caloric intake and the increase in body weight, may lead to their early pubertal development. Nutritional factors, either directly or through the regulation of nutrient-dependent hormones (e.g., insulin, leptin, IGF-1), are involved in many of the brain shaping and life events that affect the brain. Leptin may be the key link between nutritional factors and the brain, as it can influence the neural pathways projecting from the arcuate nucleus to the hypothalamus, thus affecting hypothalamic function. Fat cells produce leptin (Leptine) as a signal for fat storage, acting on the hypothalamus, when fat storage reaches a certain amount, and “allow” pubertal development 5, light pollution factors Light pollution refers to the modern society produces excessive or inappropriate light radiation, on the human life and production environment caused by the adverse effects of the phenomenon. In 2006, a questionnaire survey of children aged 6-9 years old with precocious puberty in Shenzhen showed that children with precocious puberty spent more time watching TV than the control group. The melatonin secreted by the pineal gland in human body can inhibit the release of gonadotropin from the pituitary gland, which can inhibit sexual development. When a person goes to sleep at night, the pineal gland secretes large amounts of melatonin, which stops at dawn. The human pineal gland generally develops to its peak during childhood and inhibits premature gonadal development; however, it begins to degenerate from the age of 7 to 10. Children who are exposed to too much light, such as strong lighting, long hours of television and computer monitor light, will weaken the inhibitory effect on sexual development by reducing the secretion of melatonin from the pineal gland, leading to the onset of puberty and even precocious puberty In summary, although the development of puberty is mainly determined by genetic factors, genetic factors are not a key factor for the rise in the incidence of precocious puberty However, genetic factors are not the key factor for the increase of precocious puberty. Due to the radical changes in our living environment, our endocrine system is inevitably affected. The presence of estrogen and estrogen-like environmental pollutants, lifestyle changes including the obesity epidemic and neuroendocrine changes due to stress caused by modern lifestyles all contribute to the increased incidence of precocious puberty in children. Also, environmental factors that lead to genetic mutations or the development of tumors that cause endocrine effect precocious puberty can also lead to the development of precocious puberty. Environmental and social factors become important aspects leading to the occurrence of precocious puberty. Therefore, paying attention to the understanding of factors related to the promotion of precocious puberty incidence and in-depth research on the pathogenesis of precocious puberty will not only help to treat precocious puberty, but also help to prevent precocious puberty and reduce the incidence of precocious puberty.