FSH secretion predominates in vivo and in vitro in patients with non-functioning pituitary adenomas.

OBJECTIVE: Non-functioning pituitary adenomas (NFPAs) are characterised by the lack of symptoms of hormone hypersecretory syndromes but in vitro studies have demonstrated that tumour cells may stain for gonadotrophins and/or their alpha- or beta-subunits. In this study, we aimed to examine the pattern of secretion of LH and FSH from a series of pituitary adenomas cultured in vitro and where data were available to relate the results to pre-operative serum gonadotrophin levels. METHODS: The in vitro secretion of LH and FSH was measured from 46 cultured NFPAs and compared with pre-operative serum gonadotrophin levels in 38 patients. Peritumorous 'normal' pituitary cell cultures from 20 additional pituitary tumour patients were used for comparison with the NFPA group. RESULTS: A median pre-operative LH:FSH ratio of 0.33:1 was found in 38 patients with NFPAs. Preferential secretion of FSH was also documented from media of 46 NFPAs cultured in vitro with a median LH:FSH ratio of 0.32:1. A significant correlation (r = 0.43, P < 0.01) was observed between serum and media levels of FSH but not LH. Peritumorous 'normal' pituitary cells released LH and FSH in a reversed ratio (median LH:FSH ratio = 3.6:1, P < 0.01 compared with NFPAs). CONCLUSIONS: This study has evaluated pre-operative serum gonadotrophin levels and in vitro release of hormones in cultures of surgically removed tissue from patients with NFPAs. The data suggest preferential secretion of FSH occurs both in vitro and in vivo. By demonstrating that NFPAs cultured in vitro reflect the in vivo situation of preferential secretion of FSH, it may be possible in future to perform functional studies using this system to elucidate the cellular and molecular mechanisms involved in the development of an imbalance in gonadotroph cells preferentially overproducing FSH in NFPAs.

Thyroid hormone stimulation of extracellular signal-regulated kinase and cell proliferation in human osteoblast-like cells is initiated at integrin alphaVbeta3.

The aim of the present study was to examine whether triiodo-l-thyronine (T(3)) or l-thyroxine (T(4)) rapidly activated the mitogen-activated protein kinase (MAPK) intracellular signalling cascade in osteoblast-like cells and investigate whether this activation was initiated at the integrin alpha(V)beta(3) cell surface receptor. Using PCR and western blotting, the expression of integrin alpha(V)beta(3) mRNA and protein was demonstrated in the human osteoblast-like cell lines MG-63 and SaOS-2. The treatment of MG-63 cells with T(3) (10 nM) or T(4) (100 nM) for 10 min stimulated extracellular signal-regulated kinase activity (ERK, a component of the MAPK pathway) as determined by fluorescent immunocytochemistry and an immunocomplex activity assay (T(3) by 10.7-fold, P<0.01 and T(4) by 10.4-fold, P<0.01 compared with control). T(3) (10 nM) and T(4) (100 nM) also significantly stimulated thymidine incorporation into MG-63 cells by 2.3+/-0.7-fold (P<0.01) and 2.1+/-0.1-fold (P<0.05) respectively. To establish whether transient ERK activation via the integrin alpha(V)beta(3) cell surface receptor mediated these effects, MG-63 cells were pretreated for 30 min with the specific MAPK kinase inhibitor, U0126 (1 microM), or an anti-integrin alpha(V)beta(3)-blocking antibody. Both pretreatments significantly inhibited T(3)- and T(4)-stimulated ERK activation and abolished T(3)-stimulated thymidine incorporation (P<0.01). T(4)-stimulated incorporation was significantly inhibited from 2.1- to 1.3-fold above control (P<0.05). Thus, our results suggest that T(3) and T(4) rapidly stimulate ERK activation in MG-63 cells via integrin alpha(V)beta(3) and that one functional effect of this ERK activation is increased DNA synthesis.