1983 — 1986 |
Porter, John [⬀] |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Microstructural Aspects of Creep in Alumina (Materials Research) @ University of Southern California |
0.915 |
1985 — 1986 |
Porter, John C [⬀] |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Secretion of Hypothalamic and Pituitary Hormones @ University of Texas SW Med Ctr/Dallas
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.
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0.945 |
1985 — 1987 |
Porter, John C [⬀] |
P01Activity Code Description: For the support of a broadly based, multidisciplinary, often long-term research program which has a specific major objective or a basic theme. A program project generally involves the organized efforts of relatively large groups, members of which are conducting research projects designed to elucidate the various aspects or components of this objective. Each research project is usually under the leadership of an established investigator. The grant can provide support for certain basic resources used by these groups in the program, including clinical components, the sharing of which facilitates the total research effort. A program project is directed toward a range of problems having a central research focus, in contrast to the usually narrower thrust of the traditional research project. Each project supported through this mechanism should contribute or be directly related to the common theme of the total research effort. These scientifically meritorious projects should demonstrate an essential element of unity and interdependence, i.e., a system of research activities and projects directed toward a well-defined research program goal. |
Hormone Dynamics &Target Organs in Aging Men &Women @ University of Texas SW Med Ctr/Dallas
The objectives include ascertainment of the qualitative and quantitative alterations in sex hormone production profiles in postmenopausal women and aging men as well as the consequences of these alterations. In postmenopausal women, the dominant aspect of the sex hormone production profile is decreased secretion of estradiol and increased extraglandular formation of estrone. In menopausal women, emphasis will be given to ascertaining the hormonal basis of those events that lead to hot flashes. In aging men, the dominant sex hormone production profile is decreased secretion of testosterone and increased extraglandular formation of estrogen. In both sexes, extraglandular estrogen formation increases with obesity, age, and hepatic disease. The biochemical events that underlie the development of obesity with aging and the role of the adipocyte in the conversion of C19-steroids to estrogens will be examined. The significance of estrogen in the development of androgen-induced prostatic hypertrophy in aging men and the biochemical basis of the potentiating effect of estrogen on androgen-induced prostatic hypertrophy in aging dogs will be studied. The capacity of the hypothalamus to secrete dopamine as a function of aging will be investigated in rats, including the effects of prolactin and serotonin in the stimulation and inhibition, respectively, of dopamine secretion. The role of the cellular internalization of dopamine in the processing of prolactin in lactotrophs will be studied. The subcellular localization in the aging human brain of such bioactive peptides and amines will be examined employing human brain tissue. The subcellular processing of ACTH, including its precursor molecules and metabolites, will be studied.
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0.945 |
1985 — 1996 |
Porter, John C [⬀] |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. R37Activity Code Description: To provide long-term grant support to investigators whose research competence and productivity are distinctly superior and who are highly likely to continue to perform in an outstanding manner. Investigators may not apply for a MERIT award. Program staff and/or members of the cognizant National Advisory Council/Board will identify candidates for the MERIT award during the course of review of competing research grant applications prepared and submitted in accordance with regular PHS requirements. |
Aging and Molecular Neuroendocrine Impairment @ University of Texas SW Med Ctr/Dallas
We propose to investigate the molecular basis of the impaired ability of hypothalamic dopaminergic neurons of the aged brain to synthesize L-dihydroxyphenylalanine (DOPA), to release dopamine, and to respond to prolactin stimulation. We shall investigate the hypothesis that this impaired ability is a consequence of a deficiency of exposed prolactin receptors (PR) exists in the plasma membranes of aged dopaminergic neurons compared to young dopaminergic neurons and that such a deficiency is a result of altered fludity of the lipid membranes of the neurons. To do so, the number of exposed PR in the aging hypothalamus will be evaluated using radiolabelled monoclonal antibodies to prolactin, and the effects of alterations of lipid membrane fluidity on the available number of PR will be investigated. Lipid membrane fluidity will be changed by modifying the cholesterol-to-phospholipid ratio of the membranes. The consequences of such modifications on the responses of aging neurons to prolactin stimulation will be investigated by examining the intracellular events involved in the synthesis of dopamine, the in vitro synthesis (in organ culture) of tyrosine hydroxylase (TH), the transformation of TH from an inactive form through phosphorylation to an active form, the specific activity of TH per mole of the enzyme, the synthesis of DOPA, and the release of dopamine into hypophysial portal blood. Monoclonal antibodies against TH and against PR as well as affinity-purified, monospecific polyclonal antibodies against prolactin will be utilized in these stuides. These proteins will be used in blocking experiments as well as experiments in which isolation and/or quantification of TH and PR are undertaken. The activity of TH in vivo will be assessed by quantifying the rate of synthesis of DOPA in the median eminence. The rate of release of dopamine by hypothalamic dopaminergic neurons will be quantified by determining the rate of release of dopamine into hypophysial portal blood. Using these various approaches, we propose to ascertain the extent to which down-regulation of PR in the hypothalamus of the aging brain is involved in the reduced capacity of the aged brain to synthesize DOPA and release dopamine.
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0.945 |
1987 — 1992 |
Porter, John C [⬀] |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Hormonal Control of Hypothalamic Dopamine Secretion @ University of Texas SW Med Ctr/Dallas
The longterm objective of this research is to define the hormonal, neurohormonal, and neuromodular control of the molecular and cellular mechanisms involved in the biosynthesis and release of hypothalamic dopamine. To achieve this objective, the role of ovarian steroid hormones, prolactin, vasoactive intestinal hormone, opiate-like peptides, serotonin, nerve growth factor, and inorganic cations on dopamine secretion in hypothalamic dopaminergic cells will be studied. The effect of these agents on the level of tyrosine hydroxylase (TH) mRNA, the mass of TH, the in situ enzymic activity of TH, and phosphorylation of TH in the tuberoinfundibular dopaminergic neurons as well as the release of dopamine into hypophysial portal blood will be investigated. TH mRNA will be quantified using a single stranded (32P)-labelled RNA probe complementary to TH mRNA. The radiolabelled RNA probe, cRNA, will be synthesized using TH cDNA, pTH.4, that was subcloned into the Pst I/Eco RI sites of pSP65 vector. The circular plasmid is linearized with Hind III, and the linear DNA templates transcribed with SP6 RNA polymerase. TH mRNA will be quantified using a solution hybridization/S1 nuclease assay and the (32P)cRNA probe. The mass of TH in hypothalamic dopaminergic neurons will be quantified using an immunoblot procedure and densitometric spectrometry. Purified TH will be used as the reference standard. The in situ enzymic activity of TH in hypothalamic dopaminergic neurons will be assayed using an L-dihydroxyphenylalanine (DOPA) accumulation procedure. The activity will be expressed as moles of DOPA synthesized per hr per mole of TH. The release of dopamine will be evaluated on the basis of the rate of release of dopamine into hypophysial portal blood. The findings of this study will provide insight into the mechanisms controlling neurosecretion by dopaminergic neurons of the brain. An understanding of the molecular and cellular events underlying the secretion of dopamine is of foremost importance in the development of an understanding of the development as well as the degenerative effects of aging on dopamine secreting neurons. An inability to secrete sufficient dopamine can result in Parkinsonism, a disease that afflicts one percent of all persons older than 65 years of age.
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0.945 |
1988 — 1992 |
Porter, John C [⬀] |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Impaired Secretion by Aging Neurons @ University of Texas SW Med Ctr/Dallas
neurons; secretion; aging;
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0.945 |
1993 |
Porter, John C [⬀] |
R37Activity Code Description: To provide long-term grant support to investigators whose research competence and productivity are distinctly superior and who are highly likely to continue to perform in an outstanding manner. Investigators may not apply for a MERIT award. Program staff and/or members of the cognizant National Advisory Council/Board will identify candidates for the MERIT award during the course of review of competing research grant applications prepared and submitted in accordance with regular PHS requirements. |
Aging &Molecular Neuroendocrine Impairment @ University of Texas SW Med Ctr/Dallas
We propose to investigate the molecular basis of the impaired ability of hypothalamic dopaminergic neurons of the aged brain to synthesize L-dihydroxyphenylalanine (DOPA), to release dopamine, and to respond to prolactin stimulation. We shall investigate the hypothesis that this impaired ability is a consequence of a deficiency of exposed prolactin receptors (PR) exists in the plasma membranes of aged dopaminergic neurons compared to young dopaminergic neurons and that such a deficiency is a result of altered fludity of the lipid membranes of the neurons. To do so, the number of exposed PR in the aging hypothalamus will be evaluated using radiolabelled monoclonal antibodies to prolactin, and the effects of alterations of lipid membrane fluidity on the available number of PR will be investigated. Lipid membrane fluidity will be changed by modifying the cholesterol-to-phospholipid ratio of the membranes. The consequences of such modifications on the responses of aging neurons to prolactin stimulation will be investigated by examining the intracellular events involved in the synthesis of dopamine, the in vitro synthesis (in organ culture) of tyrosine hydroxylase (TH), the transformation of TH from an inactive form through phosphorylation to an active form, the specific activity of TH per mole of the enzyme, the synthesis of DOPA, and the release of dopamine into hypophysial portal blood. Monoclonal antibodies against TH and against PR as well as affinity-purified, monospecific polyclonal antibodies against prolactin will be utilized in these stuides. These proteins will be used in blocking experiments as well as experiments in which isolation and/or quantification of TH and PR are undertaken. The activity of TH in vivo will be assessed by quantifying the rate of synthesis of DOPA in the median eminence. The rate of release of dopamine by hypothalamic dopaminergic neurons will be quantified by determining the rate of release of dopamine into hypophysial portal blood. Using these various approaches, we propose to ascertain the extent to which down-regulation of PR in the hypothalamus of the aging brain is involved in the reduced capacity of the aged brain to synthesize DOPA and release dopamine.
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0.945 |