IMMUNOREGULATORY ROLES OF LYMPHOCYTE-DERIVED PROLACTINS

Prolactin (PRL) is an anterior pituitary hormone recently found to
be a physiologic regulator of immune responses. In addition, PRL-
like molecules are synthesized by immunologically activated
murine splenocytes and may function as co-mitogens for these
cells. The experiments outlined in this application are designed to
identify the PRL-producing cell population(s) and to determine
the nature, conditions of production and co-mitogenic actions of
these PRLs. The specific aims are: 1. To identify the PRL-producing splenocyte population(s), using
the reverse plaque forming cell assay and cell surface markers to
identify individual PRL-secreting cell types. The results of these
studies will be confirmed with purified cell populations.
2. To define the mitogenic stimuli inducing PRL production in
vitro, using a variety of B-cell and T-cell mitogens and
quantitative analysis of secreted PRLs by Western blotting and
enzyme immunoassay (EIA).
3. To determine if PRL production is specific to GO-G1 or S-
phase events, by assessing PRLs in culture supernatants from
purified lymphoblasts and cells blocked in G1 phase of cell cycle.
4. To determine the effects of lymphokines and regulators of
pituitary prolactin secretion on PRL production during
lymphoproliferative events, using Western blot analysis and EIA.
5. To determine the effects of purified PRL proteins on
lymphocyte proliferation in response to T-cell and B-cell
mitogens.
6. To identify the cell population(s) responding to PRL by
increased clonal expansion, using specific cell surface markers to
enumerate each cell type. These studies will provide information essential to determine the
importance of lymphoid cell-derived PRLs in the proliferative
responses of these cells. In addition, the regulation of their
induction and secretion will be partially defined and a new PRL-
bioassay developed. These results should therefore provide
important new insight into the role of PRLs as immunoregulatory
hormones and pave the way for future studies of their in vivo
functions. Finally, in view of the evidence implicating PRL in
neoplasia and tumor cell growth, an understanding of PRL co-
mitogenesis may provide a new approach for the study of
malignant diseases in man.