The long-term goal of this work is to understand the neuroendocrine mechanisms involved in the regulation of PRL secretion. The existence of a putative novel PRF was discovered by the applicant. PRF is a small peptide found in the intermediate lobe of the pituitary. PRF is effective both in vitro and in vivo and apparently is critical for the regulation of PRL release during lactation, in the ovulatory cycle and in other conditions. The main thrust of the proposed studies will be isolation, sequencing and synthesis of ovine PP PRF. Sequential purification on HPLC columns, mass spectrometry, amino acid analysis and microsequencing will be utilized. PRF will be synthesized by a solid phase method and its biological activity validated in vitro and in vivo. Polyclonal antibodies to synthetic PRF will be generated. The distribution, function and regulation of PRF will be determined. Radioimmunoassays, ELISAs and immunocytochemical methods for studying PRF will be developed. The distribution of PRF within the hypothalamo-hypophysial system and other sites will be determined. The physiological functions of PRF will be determined using passive immunization. The factors affecting PRF release from cultured PP cells will be determined. Interactions between anterior pituitary (AP) and PP cells will be examined by co-culturing PP cells and primary AP cells or GH3 cells and examining PRL synthesis. The proliferation of lactotrophs will be examined and the subpopulation of PP cells involved will be identified.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK039551-04
Application #
3239326
Study Section
Endocrinology Study Section (END)
Project Start
1988-09-01
Project End
1992-10-31
Budget Start
1992-03-01
Budget End
1992-10-31
Support Year
4
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Indiana University-Purdue University at Indianapolis
Department
Type
Schools of Medicine
DUNS #
005436803
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
Liu, J W; Ben-Jonathan, N (1994) Prolactin-releasing activity of neurohypophysial hormones: structure-function relationship. Endocrinology 134:114-8
Corcia, A; Steinmetz, R; Liu, J W et al. (1993) Coculturing posterior pituitary and GH3 cells: dramatic stimulation of prolactin gene expression. Endocrinology 132:80-5
Dymshitz, J; Laudon, M; Ben-Jonathan, N (1992) Endothelin-induced biphasic response of lactotrophs cultured under different conditions. Neuroendocrinology 55:724-9
Dymshitz, J; Ben-Jonathan, N (1991) Effects of coculture of anterior and posterior pituitary cells on the responsiveness of lactotrophs to different secretagogues. Endocrinology 129:2535-40
Dymshitz, J; Ben-Jonathan, N (1991) Coculture of anterior and posterior pituitary cells: selective stimulation of lactotrophs. Endocrinology 128:2469-75
Murai, I; Ben-Jonathan, N (1990) Acute stimulation of prolactin release by estradiol: mediation by the posterior pituitary. Endocrinology 126:3179-84
Laudon, M; Grossman, D A; Ben-Jonathan, N (1990) Prolactin-releasing factor: cellular origin in the intermediate lobe of the pituitary. Endocrinology 126:3185-92
Laudon, M; Hyde, J F; Ben-Jonathan, N (1989) Ontogeny of prolactin releasing and inhibiting activities in the posterior pituitary of male rats. Neuroendocrinology 50:644-9
Hyde, J F; Ben-Jonathan, N (1989) The posterior pituitary contains a potent prolactin-releasing factor: in vivo studies. Endocrinology 125:736-41
Ben-Jonathan, N; Arbogast, L A; Hyde, J F (1989) Neuroendocrine [corrected] regulation of prolactin release. Prog Neurobiol 33:399-447

Showing the most recent 10 out of 14 publications