The objective of this proposal is to determine the extent and mechanisms by which the information provided by physiological pulses versus steady state gonadotropin stimulation controls the function and developmental state of ovarian tissue. This objective will be approached through use of a custom designed, unique, computer-controlled, open loop, perifusional system with capabilities for on-line data acquisition, reduction and analysis. Ovarian tissues will be obtained primarily from immature and adult rats, bu also on occasion from sheep. In particular, attempts will be made to determine the extent to which ovarian cells exhibit oscillatory activity, respond differentially to pulsatile gonadotropic signals as distinct from fixed concentrations, and involve desensitization in determining the patterns of response to the pulsatile signals. In addition attempts will be made to determine the role of agents known to act on the ovary in modulating the observed responses to pulsatile gonadotropins, and to determine the extent to which products of stimulated ovarian cells affect or control the function of other ovarian cells. Response parameters to be examined include transient changes in extracellular ions (using tubular flow-through ion-selective electrodes); cAMP and steroids (by ELISA, IRMA and RIA); membrane LH receptor (by radioligand receptor assay); and cellular interactions as assessed morphologically (by light microscopy and electron microscopy using scanning and transmission modes).

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD018018-03
Application #
3315011
Study Section
Reproductive Biology Study Section (REB)
Project Start
1985-03-01
Project End
1988-11-30
Budget Start
1987-03-01
Budget End
1988-11-30
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
Organized Research Units
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Pincus, S M; Padmanabhan, V; Lemon, W et al. (1998) Follicle-stimulating hormone is secreted more irregularly than luteinizing hormone in both humans and sheep. J Clin Invest 101:1318-24
Heinze, K; Keener, R W; Midgley Jr, A R (1998) A mathematical model of luteinizing hormone release from ovine pituitary cells in perifusion. Am J Physiol 275:E1061-71
Midgley Jr, A R; McFadden, K; Ghazzi, M et al. (1997) Nonclassical secretory dynamics of LH revealed by hypothalamo-hypophyseal portal sampling of sheep. Endocrine 6:133-43
Padmanabhan, V; McFadden, K; Mauger, D T et al. (1997) Neuroendocrine control of follicle-stimulating hormone (FSH) secretion. I. Direct evidence for separate episodic and basal components of FSH secretion. Endocrinology 138:424-32
Cantor, H C; Padmanabhan, V; Favreau, P A et al. (1996) Use of newly designed microperifusion system with amperometric sensors for near-continuous on-line monitoring of hormone secretion. I. correlation with the luteinizing hormone secretory response to gonadotropin-releasing hormone. Endocrinology 137:2782-90
Wiesen, J F; Midgley Jr, A R (1994) Expression of connexin 43 gap junction messenger ribonucleic acid and protein during follicular atresia. Biol Reprod 50:336-48
Brand, R M; Ghazzi, M N; Rolfes-Curl, A et al. (1994) Continuous on-line hydrogen ion monitoring to study flow dynamics of perifusion systems and cellular metabolism. Am J Physiol 266:E739-49
Brand, R M; Midgley, A R; Williams, W J (1994) Convolution: a method for data analysis in perifusion systems. Am J Physiol 267:E759-68
Brand, R M; Lyons, R H; Midgley, A R (1994) Understanding the dynamics of cellular responsiveness to modifications of metabolic substrates in perifusion. J Cell Physiol 160:10-6
Wiesen, J F; Midgley Jr, A R (1993) Changes in expression of connexin 43 gap junction messenger ribonucleic acid and protein during ovarian follicular growth. Endocrinology 133:741-6

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