Our long range objectives have been to clarify the role of neuroendocrine, hormonal, and genetic factors on growth and maturation, to elucidate the pathogenesis of neuroendocrine, endrocine, and genetic disorders which derange these processes and to contribute to advances in prevention, diagnosis, management and treatment of such disorders. Our efforts will be directed to: 1) continue studies on the factors which affect adrenal androgen secretion, to exploit a newly developed primary human adrenal cortex cell culture system as an in vitro bioassay in search of a postulated adrenal androgen stimulating factor and to clarify the relationship of adrenarche to gonadarche and the role of adrenal androgens in growth and sexual maturation; 2) to elucidate the neuroendocrine mechanisms involved in the control of puberty, to examine the role of neurotransmitter and neuromodulator systems in the restraint of the onset of puberty, to replicate the pubertal pattern of gonadotropin and sex steroid secretion by the pulsatile administration of synthetic LRF, to assess the significance of changes in serum and urinary B/I ratio of LH in puberty and its disorders and to assess the usefulness of a superagonist of LRF in the treatment of true precocious puberty; 3) to extend studies on the neuroendocine regulation of hormonal secretion in the fetus; to consider the role of neuroamine regulatory systems and neurotransmitters in the release of gonadotropins and LRF in the ovine fetus, to assess the development of the hypothalamic pituitary feedback system for sex steroids in the ovine fetus, to study the ontogeny of pituitary receptors for LRF, to consider the relationship of GH levels in the fetus to secretion of somatostatin (SRIF), to assess the modulation by SRIF of the neuroamine regulation of GH secretion in the fetus, to elucidate the ontogoney of liver receptors for GH receptors and to investigate the regulation of somatomedin synthesis and secretion in the fetus; 4) to extend studies on the role of perinatal events, CNS trauma and CNS irradiation on the induction of hypothalamic hypopituitarism, to elucidate the inheritance pattern of GH deficiency, to assess in children with presumed abnorlities of GH metabolism, the biologic and immunologic activity of endogenous GH and somatomedin; 5) to clarify the interrelationship of sex chromosome constitution and phenotype in gonadal dysgenesis.
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