Immunodetection of glycoprotein hormone subunits in nonfunctioning and glycoprotein hormone-secreting pituitary adenomas

Abstract

While it is established that nonfunctioning pituitary adenomas (NFPA) produce a spectrum of glycoprotein hormones, the ability of glycoprotein hormone-secreting adenomas to synthesize hormones other than those in vivo hypersecreted has been poorly investigated so far. In this study the immunolocalization of the beta-subunits of LH, FSH, CG and TSH and the common alpha-subunit was investigated in 10 NFPA, 3 gonadotropin-secreting adenomas (Gn-omas, 1 LH-oma, 1 FSH-oma and 1 LH/FSH-oma) and 3 TSH-secreting adenomas (TSH-omas) using an immunohistochemical technique with specific antibodies to glycoprotein subunits. The percentage of positive cells was determined observing at least 5 photograph fields containing about 50 cells. Nine of the 10 NFPA were positive for FSH beta with a high percent of positive cells (> or =30%), 6 for LH beta and 5 for TSH beta with a lower number of labelled cells (from 5 to 30%). Of the 8 NFPA tested, 5 showed a marked positivity for CG beta. In Gn-omas, tumors were positive for the gonadotropin that was in vivo hypersecreted (10-60% positive cells) and negative for either TSH beta or CG beta. Similarly, in TSH-omas TSH beta was detected in a variable proportion of cells (10-30%) with no immunoreactivity for either LH beta or FSH beta or CG beta. This study indicates that the coexpression of FSH beta, LH beta, CG beta and TSH beta molecules is characteristic of NFPA since Gn-omas were negative for CG beta and TSH beta and TSH-omas were negative for FSH beta, LH beta and CG beta. Moreover, the biological events that make NFPA 'silent' glycoprotein hormone-secreting adenomas remain unclear since the positivity for gonadotropins and TSH showed by NFPA was similar to that observed in Gn-omas and TSH-omas, respectively.

Beta human chorionic gonadotropin (β-hCG) expression in pituitary adenomas: relationship to endocrine function and tumour recurrence

“…Discussion b-hCG expression by pituitary adenomas is described, although its relevance, notably its relationship to the endocrine function of the tumour, markers of cellular proliferation or tumour recurrence is less clear [4,5,16,19]. In the present study, we observed that the majority of pituitary adenomas exhibited b-hCG immunopositivity, although this was more apparent with NFPA (91%) than functioning pituitary adenomas (80%).…”

“…The presence of hCG in pituitary adenomas has been described previously, although the numbers of cases studied were small and varying degrees of b-hCG expression were observed [13,16,19,23]. Using in situ hybridisation techniques, Levy and co-workers described b-hCG expression in 2 of 35 (6%) pituitary adenomas [7].…”

“…Moreover, it has been suggested that low levels of hCG may be released from the pituitary in a pulsatile fashion in normal males and non-pregnant females, although the physiological significance of this is not known [6,7,12,20]. b-hCG has also been shown to be produced normally by the testis in males [19,21] and the fallopian tubes in females [22]. In pathology, a number of malignancies, including teratomas, choriocarcinomas and islet cell tumours release hCG, and indeed b-hCG is a valuable tumour marker in these conditions [10,11].…”

Growth hormone-releasing hexapeptide (GHRP-6) increases intracellular calcium concentrations in cultured cells from human pituitary adenomas of different types

“…In tumours other than GH-omas immunoreactivity for GH was either absent or present only in a small number of cells (<5% of total cells, data not shown). Morphological data of NFPA have been reported previously elsewhere (25).…”

Effect of TRH on beta-gonadotropin subunits in patients with pituitary microincidentalomas

“…Whereas compelling evidence exists that pituitary macroadenomas express the b-FSH and the b-LH genes and, indeed, increase the release of these peptides when exposed to TRH in vitro (11,17,18), this is the first report to suggest that adenomatous cells comprising pituitary microincidentalomas possess a similar biosynthetic capacity. Definitive proof will obviously depend on the identification of these peptides in vitro by immunohistochemistry, the detection of b-FSH/b-LH mRNA, or the release of gonadotropin b-subunits in in vitro studies, as previously reported in pituitary macroadenomas.…”