Increased lactotrophs despite decreased somatotrophs in the dwarf (dw/dw) rat: a defect in the regulation of lactotroph/somatotroph cell fate?

Abstract

The dwarf (dw/dw) rat differs from all other rodent models of GH deficiency in that its pituitary prolactin (PRL) content is normal or even increased. We have now studied this throughout postnatal development, using a combination of immunocytochemistry, RIA and fluorescenceactivated cell sorting (FACS) and analysis. Compared with normal Albino Swiss (AS) rats, adult dw/dw rats showed a profound reduction in pituitary GH content accompanied by increased PRL content, significantly so in females (AS vs dw/dw; P<0·01). Somatotroph hypoplasia was evident in the adult dw/dw rats, with most GH +ve cells showing weak immunostaining, whereas many more strongly stained PRL cells were evident in pituitary sections from dw/dw rats. FACS analysis confirmed both somatotroph hypoplasia and relative lactotroph hyperplasia in dw/dw rats at all ages studied (9-144 days); the difference in somatotrophs increased with age whereas the difference in lactotrophs declined with age. At 9 days, the percentage of lactotrophs was 10-fold higher in dw/dw rats than in AS rats. Young dw/dw rats also had a higher proportion of mammosomatotrophs than AS rats, although this difference disappeared as the mammosomatotroph proportions increased with age in both strains. GHRH released GH from both dw/dw and AS cells maintained in culture for 5 days. The sensitivity to GHRH and the amount of GH released was lower in the dw/dw cultures, mostly explained by their fewer GH cells and lower initial GH content. GHRH increased cAMP in AS but not in dw/dw cultures, even when these were greatly enriched for dw/dw somatotrophs by FACS sorting prior to culture. These results suggest that GHRH-induced cAMP stimulation is required for trophic effects on GH synthesis and somatotroph proliferation, but is not required for GHRH-stimulated GH release. The inverse changes in somatotroph and lactotroph numbers suggest that the dw/dw mutation disturbs the mechanism that specifies and retains appropriate numbers of somatotrophs in their differentiated state, and results in a higher proportion of the remaining cells progressing to lactotrophs. The dw/dw phenotype is thus not confined to somatotrophs.

Identification and enrichment of colony-forming cells from the adult murine pituitary

“…These properties have been shown previously to reflect size and granularity, respectively, of cells isolated from the pituitary and other tissues [21,23]. Forward and side scatter profiling of AMCA + cells revealed three populations: small agranular cells (P1), larger agranular cells (P2), and large granular cells (P3; Fig.…”

Independent differentiation of mammotropes and somatotropes in the chicken embryonic pituitary gland

“…With development, the cells spread to both lobes, and no difference between cell densities in the cephalic and caudal lobes was found. Bar 100 lm on results of morphological experiments on the differentiation of mammotropes have also been reported (Begeot et al 1984;Tierney et al 2002). They claimed that these contradictory results may be due to error in technique of double staining method or the used antibodies.…”

“…In addition, the existence of somatomammotropes (SMTs), cells that produce both GH and Prl, and establishment of cell lines that produce both hormones are strong evidence for this transdifferentiation (Goluboff et al 1969;Frawley et al 1991;Inoue et al 1991;Chaidarun et al 1994). On the other hand, contrary results have cast doubt on the existence of SMTs and differentiation of somatotropes into mammotropes (Begeot et al 1984;Tierney et al 2002).…”

Membrane estrogen receptor-α levels in MCF-7 breast cancer cells predict cAMP and proliferation responses

“…Elevated levels of intracellular cAMP can inhibit the growth of some cell types but stimulate the growth of others. Among the cell types whose growth is stimulated by cAMP are thyroid [6], pituitary [7], and normal human breast epithelial cells in culture [8]. Several studies have demonstrated that cAMP inhibits the growth of established breast cancer cell lines and breast cancer cells in primary culture [8-10].…”