Abnormal response of luteinizing hormone beta subunit to thyrotrophin‐releasing hormone in patients with non‐functioning pituitary adenoma

Gil-Del-Alamo, Paloma; Pettersson, Kim; Saccomanno, K.; Spada, Anna; Faglia, G.; Beck‐Peccoz, Paolo

doi:10.1111/j.1365-2265.1994.tb01833.x

Cited by 32 publications

(22 citation statements)

References 17 publications

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“…The dissociated secretion of CG-/? subunit and intact CG molecule in patients with pituitary tumors is in line with previous observations indicating imbalanced biosynthesis of intact glycoproteins and free subunits by pituitary tumoral cells (21)(22)(23)(24)(25). Secretion of uncombined a-or /3-subunits of pituitary glycoprotein molecules has been recognized with increasing frequency in pituitary tumors.…”

Section: Discussionsupporting

confidence: 79%

Serum levels of β-subunit of chorionic gonadotropin in patients with pituitary tumors

Gil-Del-Alamo

Saccomanno

Lania

et al. 1995

European Journal of Endocrinology

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Many studies have shown that normal and tumoral pituitary is able to synthesize chorionic gonadotropin (CG). The aim of the present work was to investigate the circulating levels of free beta-subunit of CG (CG-beta) in a large number of patients with pituitary tumors in basal conditions and after thyrotropin-releasing hormone (TRH) injection. The study includes 27 healthy subjects, 23 patients with prolactinoma, 20 with growth hormone-secreting adenoma and 77 with non-functioning pituitary adenoma (NFPA). The CG-beta was evaluated using a new one-step immunometric assay employing two monoclonal antibodies directed against epitopes present only on the free CG-beta and showing a detection limit of 0.04 U/l and a cross-reactivity with complete CG < 0.01%. In basal conditions, serum CG-beta was undetectable in healthy subjects and in the majority of patients, while in seven patients with NFPA and four with prolactinoma the CG-beta values ranged between 0.05 and 0.72 U/l. In these 11 patients serum levels of intact CG were found within the normal range (normal range < 5 U/l), while two patients with NFPA and one with prolactinoma had levels of free alpha-subunit inappropriately high with respect to gonadotropins and thyrotropin. Injection of TRH caused CG-beta to increase in two out of 16 patients with NFPA, whereas it was ineffective in 12 healthy subjects and 10 patients with prolactinoma. The present data indicate that detectable level of CG-beta not associated with hypersecretion of the intact CG molecule may be observed in about 10% of patients with NFPA or prolactinoma, while abnormal CG-beta responses to TRH are observed infrequently in individual patients with NFPA.

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Section: Discussionsupporting

confidence: 79%

Serum levels of β-subunit of chorionic gonadotropin in patients with pituitary tumors

Gil-Del-Alamo

Saccomanno

Lania

et al. 1995

European Journal of Endocrinology

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“…In patients with gonadotropin levels consistent with postmenopausal status, the presence of a gonadotropinoma was considered unlikely on the basis of the simultaneous elevation of both LH and FSH, which is unusual in this type of tumor, and/or absence of abnormal gonadotropin response to TRH, which characterizes gonadotropinomas (19,20). However, since gonadotropinomas and NFPA share a number of biochemical and morphological characteristics (14,15,(19)(20)(21)(22), this possibility cannot be excluded. From the analysis of data obtained in normal subjects and in patients with NFPA in the 50-80 year age range, accuracy of FSH and LH measurement for the diagnosis of NFPA was very high, both FSH and LH showing a high sensitivity and specificity (about 90%).…”

Section: Discussionmentioning

confidence: 99%

“…All patients had normal levels of the a-subunit (0.8-4.2 U/l in women and 0.2-0 in men). Body mass index (BMI) was normal (range [18][19][20][21][22][23][24]. The nature of the study was explained to the subjects before they gave their voluntary informed consent.…”

Section: Subjectsmentioning

confidence: 99%

Effect of aging on serum gonadotropin levels in healthy subjects and patients with nonfunctioning pituitary adenomas

et al. 2000

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Objective: Nonfunctioning pituitary adenomas (NFPA), which represent about one-quarter of human pituitary tumors, occur in middle or old age. Determination of gonadotropin levels, which are not expected to be high during the early postmenopause in normal women and which are low in women with NFPA, is important to distinguishing hypogonadal status due to the normal decline of gonadal function from that due to hypothlalamic-pituitary dysfunction. The aim of the study was to verify whether this difference still persists in old subjects, despite the physiological decline of gonadotropins in the last decades of life. Design and methods:The study included 154 healthy subjects (aged 50-104 years) and 47 patients with NFPA (aged 50-80 years). Blood samples were collected after an overnight fast and hormone levels were measured by two immunofluorimetric assays. Results: In healthy women the highest serum levels of gonadotropins were present in the 50-60 year age group, with a slight but progressive age-associated decrease in serum FSH and LH being observed thereafter. In healthy men serum gonadotropin levels were stable up to 70 years, increased up to 75-85 years and thereafter gradually decreasing. Female patients with NFPA showed levels of gonadotropins which were far lower than controls. Only three patients had levels of both FSH and LH above the 2.5 centile for normal subjects. A high sensitivity and specificity of gonadotropin measurements (about 90%) for the diagnosis of NFPA was observed in female patients aged 50-80 years. In male subjects, a large overlap of gonadotropin values in NFPA and controls, namely over the 50-70 years age range, was observed. Conclusions: Our study demonstrates that despite the gradual decline of gonadotropin levels in healthy postmenopsausal women, the reduction of both FSH and LH persists in old patients with NFPA, suggesting that measurement of gonadotropin levels could prove useful in the evaluation of pituitary lesions even in old women. More subtle differences seem to occur in male subjects.

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“…Monomorphous adenomas are defined as those that synthesize two or more hormones in the same cell. In bimorphous and plurimorphous adenomas, each hormone is produced by different cell populations, and almost all possible combinations of hormone productions involving GH and PRL, GH, PRL, glycoprotein hormone subunit ( GSU), TSH or FSH have been observed (Felix et al 1994, Furuhata et al 1994, Gessl et al 1994, Gil-del-Alamo et al 1994, Bertholon-Gregoire et al 1999. Although these combinations of hormones correspond to the differentiation of the cell lineages, it has been reported that very occasional cases of bimorphic pituitary adenomas produce adrenocorticotropic hormone (ACTH) and GH in different cell populations (Arita et al 1991, Kovacs et al 1998.…”

Section: Introductionmentioning

confidence: 99%

Exogenous expression of Pit-1 in AtT-20 corticotropic cells induces endogenous growth hormone gene transcription

Kurotani

Yoshimura²,

Iwasaki³

et al. 2002

Journal of Endocrinology

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The pituitary-specific POU-homeodomain transcription factor, Pit-1, is known to regulate the expression of the GH gene in somatotropes, prolactin (PRL) in lactotropes, and TSH in thyrotropes. It is not normally expressed in corticotropes or gonadotropes. We addressed the question of whether exogenous Pit-1 was sufficient to induce ectopic transcription of the GH gene in the corticotropic cell line, AtT-20, or the gonadotropic cell line, T3-1. A fusion gene composed of enhanced green fluorescent protein gene and human Pit-1 cDNA was transfected into AtT-20 and T3-1 cells. The endogenous mouse GH mRNA was induced in three of nine AtT-20 cell lines and one of three T3-1 cell lines containing the fusion gene. A small amount of GH protein was also detected in these cell lines. These data indicate that transfected Pit-1 is capable of inducing transcription of the GH gene in AtT-20 cells and T3-1 cells. These data also suggest that synergistic co-factors might be required to transcribe the GH gene effectively for translation into GH protein. Furthermore, our findings support the hypothesis that the function of anterior pituitary cells is determined by the combinatorial action of specific transcription factors.

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Abnormal response of luteinizing hormone beta subunit to thyrotrophin‐releasing hormone in patients with non‐functioning pituitary adenoma

Cited by 32 publications

References 17 publications

Serum levels of β-subunit of chorionic gonadotropin in patients with pituitary tumors

Serum levels of β-subunit of chorionic gonadotropin in patients with pituitary tumors

Effect of aging on serum gonadotropin levels in healthy subjects and patients with nonfunctioning pituitary adenomas

Exogenous expression of Pit-1 in AtT-20 corticotropic cells induces endogenous growth hormone gene transcription

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