Using microcannulation procedures, we propose (1) to investigate under in vivo conditions the mechanisms whereby anterior and posterior pituitary hormones are secreted into pituitary stalk blood resulting in super-high concentrations in stalk plasma of LH, FSH, TSH, prolactin, ACTH, alpha-MSH, and vasopressin; (2) to determine the role of posterior pituitary hormones in the control of anterior pituitary hormone secretion; (3) to investigate the role of thyroid hormones, gonadal steroids, and adrenal steroids in the secretion of pituitary hormones into stalk blood; (4) to investigate the significance of retrograde blood flow in the pituitary stalk in the delivery of pituitary hormones to, and their transport across, the median eminence and hence to the brain; (5) to determine the mechanisms involved in the hypothalamic secretion of LHRH, TRH, and dopamine into hypothalamic-hypophysial portal blood. Using in vitro conditions, we propose (1) to characterize the subcellular compartmentalization of LHRH, TRH, and alpha-MSH in synaptosome-like particles, hereafter called synaptosomes, prepared from hypothalamic homogenates; (2) to investigate the mechanisms involved in the storage and release of LHRH, TRH, and alpha-MSH from synaptosomes; (3) to test the hypothesis that Ca 2 ion in the presence of depolarizing concentrations of K ion causes TRH, LHRH, and alpha-MSH release from synaptosomes by activating guanylate cyclase and/or adenylate cyclase, thereby forming cGMP and/or cAMP; (4) to investigate the role of synaptosomal microtubules, tubulin, and microfilaments in the exocytosis of TRH, LHRH, and alpha-MSH; (5) to investigate the role of prostaglandins, viz., PGE2 and PGF2 alpha, prostaglandin precursors, and phospholipids enriched with arachidonic acid and lysophospholipids in the release of TRH, LHRH, and alpha-MSH from synaptosomes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIADDK)
Type
Research Project (R01)
Project #
5R01AM001237-30
Application #
3150677
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1977-09-01
Project End
1987-08-31
Budget Start
1985-09-01
Budget End
1986-08-31
Support Year
30
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Type
Schools of Medicine
DUNS #
City
Dallas
State
TX
Country
United States
Zip Code
75390
Milewich, L; Madden, J D; Gomez-Sanchez, C E (1992) 5 alpha-androstane-3,17-dione in peripheral plasma of men and women. J Steroid Biochem Mol Biol 41:185-90
Milewich, L; Sontheimer, R D; Herndon Jr, J H (1990) Steroid sulfatase activity in epidermis of acne-prone and non-acne-prone skin of patients with acne vulgaris. Arch Dermatol 126:1312-4
Wang, P S; Gonzalez, H A; Reymond, M J et al. (1989) Mass and in situ molar activity of tyrosine hydroxylase in the median eminence. Effect of thyroidectomy and thyroid hormone replacement. Neuroendocrinology 49:659-63
Porter, J C; Wang, P S; Kedzierski, W et al. (1989) Quantification of the mass of tyrosine monooxygenase in the median eminence and superior cervical ganglion. Methods Enzymol 168:371-85
Sissom, J F; Eigenbrodt, M L; Porter, J C (1988) Anti-growth action on mouse mammary and prostate glands of a monoclonal antibody to prolactin receptor. Am J Pathol 133:589-95
Wang, P S; Gonzalez, H A; Porter, J C (1988) Saline ingestion stimulates the in situ molar activity of tyrosine hydroxylase in the median eminence and superior cervical ganglion. Brain Res 446:363-8
Gonzalez, H A; Porter, J C (1988) Mass and in situ activity of tyrosine hydroxylase in the median eminence: effect of hyperprolactinemia. Endocrinology 122:2272-7
Milewich, L; Shaw, C B; Sontheimer, R D (1988) Steroid metabolism by epidermal keratinocytes. Ann N Y Acad Sci 548:66-89
Faucher, D J; Lowe, T W; Magness, R R et al. (1987) Vasopressin and catecholamine secretion during metabolic acidemia in the ovine fetus. Pediatr Res 21:38-43
Milewich, L; Porter, J C (1987) In situ steroid sulfatase activity in human epithelial carcinoma cells of vaginal, ovarian, and endometrial origin. J Clin Endocrinol Metab 65:164-9

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