Our long range objectives have been to determine that pathogenesis of neuroendocrine, endocrine and genetic disorders which derange processes of growth and maturation and to contribute to the knowledge of prevention, diagnosis, management and treatment of these disorders. Our efforts will be directed to: 1) elucidate the biologic effect of synthetic somatomedin-C in normal adults and in children with disorders of growth, particularly those resistant to GH therapy (Laron dwarfism and GH deficient patients with high ab to hGH); to assess the role of IGF-I and IGF-II in the regulation of GH secretion; to determine the pattern of secretion of GRF in children and adults and the factors which regulate GRF secretion; to assess the role of GH on feedback and response to GRF; to consider the possibility that GH deficient patients may have a syndrome of resistance to GRF; to extend studies on the long term effect of final height of growth hormone therapy in non-GH deficient children; and to continue in vitro studies on the effect of sex steroids, dexamethasone and T3 on the release of GH and GH mRNA synthesis utilizing dispersed bovine pituitary cells. 2) To elucidate the role of a newly synthesized gonadal peptide in the regulation of gonadotropin secretion from fetal life to the adolescent period; to continue studies on the pathophysiology of puberty and to assess the long term effects of superagonists of LRF in the treatment of precocious puberty on GH and SMC/IGF-I secretion, bioactive/immunoactive gonadotropins, and final height; to identify the intratesticular defect in males with an inherited form of sexual precocity, familial testotoxicosis and to continue efforts to identify an adrenal androgen stimulating hormone (AASH). 3) To extend studies on the neuroendocrine 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 role of fetal gonadal, maternal and placental steroids; to investigate the ontogenesis of fetal testicular steroidogenic enzymes, the factors which regulate their development and by in situ hybridization to identify their cellular localization; to extend study on the ontogenesis of GRF and SRIF in the ovine fetus by in vitro and in vivo techniques; to assess the maturation of the inhibitory action of SRIF on GH release; to elucidate the role of somatomedin in the normal and growth retarded ovine fetus and its effect on regulation of pituitary and placental hormone secretion.
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