Endocrine Relationships Preceding Precocious Puberty (pilot)

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Genotype, level of nutrition, metabolic signals, adiposity, and growth rate all have profound influence on the neuroendocrine system that regulates hypothalamic-pituitary-gonadal axis (HPGA) in mammals. These factors can modify the rate of sexual maturation and age at first ovulation (puberty). It is not fully understood which of these factors has a predominant influence on reproductive development. Central precocious puberty (CPP) is a phenomonen that has been clinically studied since the latter half of the 19th century and involves the premature reemergence of gonadotropin-releasing hormone (GnRH) secretion during childhood, activating a cascade of pituitary-gonadal and physical maturation. Clinical conditions of CPP involve thelarche, menarche, and acceleration of linear growth and bone maturation. Racial differences exist in sexual maturation with 48% of African-American, ¿ 25% of Hispanic, and 15% of white girls exhibiting secondary sexual characteristics by age 8. Girls whose thelarche begins between 2 and 6 yr of age often have rapidly progressive pubertal development consistent with CPP. True CPP is of concern because of underlying disorders that may be causing premature sexual development. The dramatic psychosocial implications of CPP are troubling, as there is no natural progression into the teenage years. The current clinical treatment for patients with CPP is administration of long acting GnRH agonists. The long-term aim of this research program is to elucidate developmental relationships between reproduction and growth in developing females and identify specific endocrine signals that influence the occurrence of CPP. The specific aim of this pilot project is to investigate chronic GnRH administration in a bovine animal model with precociously induced puberty to contribute to the understanding of mechanisms underlying the onset of puberty in female mammals. Proposed research is designed to establish reproductive, growth, and endocrine characteristic of these precocious females. Chronic GnRH administration, by osmotic pump, will suppress the HPGA (via lower gonadotropin and gonadal steroid secretion) in an animal model that has been induced to exhibit precocious puberty and enhanced adiposity. Results will provide metabolic, growth, and endocrine relationships that exist in females with CPP, and serve as a basis for future research projects to further our understanding of reproductive development and facilitate alternative clinical therapies for CPP.