An exciting new field of research opens with the novel hypothesis supported herein by preliminary data that human cells for connective tissue (CT) synthesize the protein hormone prolactin (Pr1) in response to pathologic situations. Unlike the endocrine source from the pituitary (pit) gland, ctPtl is proposed to act as auto- and para-crine hormone that binds specific membrane receptors (R) and functions by modulating polyamines and prostaglandins and the effects of various other hormones. Our previous decade-long investigation discovered uterine (ut) tissues serves as de novo sources of Prl; endo- and myometrium, decidua and fibroids. Consistent with the new hypothesis, ut tissue is now preceived as a special case of CT stimulated to produce utPrl during physiological yet 'stressful' (inflammatory) states, the menstrual cycle and pregnancy. In the planned 2-year study, normal and pathologic CT from surgical patients (male and female) will be grown in cell (primary and passaged) and explant cultures. Prl antigen in conditioned media and within cells will be monitored by radioimmunoassay (RIA) and immunohistochemistry (IHC), respectively. Paraffin-preserved surgical and autopsy tissues will be analyzed for 'in vivo' ctPrl by IHC. Biological stimulators of ctPrl will be sought (pH, %CO2, soluble factors from microorganisms including endotoxin, female steroids and prostaglandins). Parameters of ctPrl will be determined and compared with pit- and utPrl(s): molecular size and charge (G-100 gel and ionic exchange column chromatography), antigenicity (parallel titration curves by RIA technique) and function (enhanced proliferation of lymphoma cells in vitro). Prior evidence supported the theory that one genome coded pit- and utPrl(s) albeit separate mechanisms controlled Prl synthesis. Incorporation of 3H-leucine into immunoprecipitated ctPrl will confirm de novo synthesis by cultured CT cells (CTC). Future studies will determine the potential of isolated CTC subpopulations to synthesize Prl, identify the CTC type (IHC and light- and electron microscopy) that produces Prl, elucidate the control mechanism of ctPrl synthesis and the role of Prl R therein, define the function of ctPrl in pathology (CT and nonCT tumors, formation of adhesions and keloids) and healing (wound repair, renewal of shed uterine lining; tissue defense, encapsulation of infectious agents and cancer by CT) including differentiation and interconversion of CTC, and discover pharmacological means to modulate ctPrl to clinically minimize adhesion formation, enhance wound repair, and control infection and cancer growth.
| Chapitis, J; Betz, L M; Brumsted, J R et al. (1989) Observation of production of immunoactive prolactin by normal human connective tissue in cell culture. In Vitro Cell Dev Biol 25:564-70 |
| Chapitis, J; Riddick, D H; Betz, L M et al. (1988) Physicochemical characterization and functional activity of fibroid prolactin produced in cell culture. Am J Obstet Gynecol 158:846-53 |
