Previous studies have demonstrated that the neuropeptides GnRH, DSIP a
nd TRH induce LH and TSH differentiation in a dose-dependent manner. T
hese studies have shown that a single hypothalamic hormone can induce
the differentiation of more than one cell type, and conversely that on
e pituitary cell can differentiate under the influence of more than on
e hypothalamic factor. In the present study, our experimental in vitro
model was used to demonstrate that these hypothalamic factors are abl
e to influence LH and TSH cell appearance by a synergistic action. Pit
uitary primordia of 11 day-old rat embryo were cultured in a synthetic
medium. Four different combinations were tested by adding either DSIP
, GnRH and TRH together, or any combination of two of them in the cult
ure medium, each at a concentration of 10(-15) M. The expression of di
fferent pituitary phenotypes was estimated as the percentage of immuno
reactive area per section of cultured pituitary. The medium supplement
ed with the three peptides at 10(-15) M was more efficient for the dif
ferentiation of LH and TSH than the other media combinations including
only two peptides. These results confirm that the LH and TSH cell dif
ferentiation can be induced by a synergistic mechanism involving sever
al neuropeptides. Such a mechanism, already demonstrated for somatotro
pes, could prevail in in vivo pituitary cell differentiation.