The mechanism of growth-promoting effects of prolactin in embryogenesis - Links to growth factors

The polypeptide hormone prolactin (PRL) has been implicated in the regulati on of embryonic growth and development, but the control mechanisms involved in the effects of the hormone are poorly understood. Several investigators suggested that there may be a possible link between the effects of PRL and insulin-like growth factors (IGFs). Recent studies have also shown that li gand-induced activation of PRL receptors leads to tyrosine phosphorylation of multiple intracellular proteins, and tyrosine kinase activation takes pl ace in mediating the mitogenic action of PRL. In order to determine whether IGFs are involved in mediating the growth-promoting effect of PRL, rat emb ryos were culture in vitro for 48 h in whole rat serum and serum depleted o f low molecular weight molecules (30 kD retenate) supplemented with rat PRL in the presence and absence of antisera against rat PRL, IGF I and IGF II. To investigate the effects of inhibiting the signal transduction of the PR L receptors, the embryos were preincubated for 2 h in retenate in the prese nce of tyrosine kinase inhibitors, tyrphostin 47 and genistein, then rat PR L was added to the culture medium. Embryos cultured in retenate showed seve re growth retardation, and the addition of rat PRL caused significant incre ase in growth and development of the embryos suggesting that embryos may be able to utilize maternally derived PRL during organogenesis. The presence of antiserum against rat PRL abolished the PRL-induced increase in developm ent and antibodies against IGF I and II had a similar effect,, suggesting t hat IGFs may be involved in the effect of the hormone. The 2-hour preincuba tion with genistein and tyrphostin also abolished the PRL-induced increase in development. These results indicate that functional PRL receptors are pr esent in rat embryos at this stage which may play an important role in the control of growth and development and this may be linked to growth factors and their receptors.