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Haruyoshi Nakao, Masafumi Koga, Masayo Arao, Makoto Nakao, Bunzo Sato, Susumi Kishimoto, Yoichi Saitoh, Norio Arita and Shintaro Mori

Abstract. We have performed an enzyme-immunoassay for estrogen receptor on 56 human pituitary adenomas and compared the results with a single point estradiol binding assay. There was a significant positive correlation between the two assays of cytoplasmic estrogen receptor (r = 0.960). Normal human pituitaries (N = 2) had an estrogen receptor concentration of 17 fmol/mg protein by enzyme-immunoassay. Of 14 prolactinomas, 6 (43%) contained estrogen receptor with a concentration of 33.5 ± 7.4 (mean ± sem) fmol/mg protein. Six of 11 (55%) macroprolactinomas were estrogen receptorpositive, whereas all 3 microprolactinomas were estrogen receptor-negative. Only one (13%) of 8 GH- and PRL-secreting adenomas, and 3 of 6 (50%) gonadotropin-secreting adenomas were estrogen receptor-positive; the latter had a concentration of 13.5 ± 1.6 fmol/mg protein. Estrogen receptor was not detected in 21 pure GH-secreting adenomas and 7 nonsecreting adenomas. These results demonstrate the precise frequency of estrogen receptor in various human pituitary adenomas, since enzyme-immunoassay as well as single point estradiol binding assay could detect estrogen receptor even in small specimens. Enzyme-immunoassay is suitable for evaluation of estrogen receptor status in human pituitary adenomas.

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Masafumi Koga, Haruyoshi Nakao, Masayo Arao, Bunzo Sato, Keizo Noma, Yasuhiko Morimoto, Susumu Kishimoto, Shintaro Mori and Toru Uozumi

Abstract. Dopamine receptors on human pituitary adenoma membranes were characterized using [3H] spiperone as the radioligand. The specific [3H]spiperone binding sites on prolactin (PRL)-secreting adenoma membranes were recognized as a dopamine receptor, based upon the data showing high affinity binding, saturability, specificity, temperature dependence, and reversibility. All of 14 PRL-secreting adenomas had high affinity dopamine receptors, with a dissociation constant (Kd) of 0.85 ±0.11 nmol/l (mean ± sem) and a maximal binding capacity (Bmax) of 428 ± 48.6 fmol/mg protein. Among 14 growth hormone (GH)-secreting adenomas examined, 8 (57%) had dopamine receptors with a Kd of 1.90 ± 0.47 nmol/l and a Bmax of 131 ± 36.9 fmol/mg protein. Furthermore, 15 of 24 (58%) nonsecreting pituitary adenomas also had dopamine receptors with a Kd of 1.86 ± 0.37 nmol/l and a Bmax of 162 ± 26.0 fmol/mg protein. These results indicate that some GH-secreting adenomas as well as some nonsecreting pituitary adenomas contain dopamine receptors. But their affinity and number of binding sites are significantly lower (P < 0.05) and fewer (P < 0.001) respectively, than those in PRL-secreting adenomas.

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Hitoshi Nishizawa, Genzo Iguchi, Ayumi Murawaki, Hidenori Fukuoka, Yoshitake Hayashi, Hidesuke Kaji, Masaaki Yamamoto, Kentaro Suda, Michiko Takahashi, Yasushi Seo, Yoshihiko Yano, Riko Kitazawa, Sohei Kitazawa, Masafumi Koga, Yasuhiko Okimura, Kazuo Chihara and Yutaka Takahashi


Liver dysfunction in adult hypopituitary patients with GH deficiency (GHD) has been reported and an increased prevalence of nonalcoholic fatty liver disease (NAFLD) has been suggested.


The objective of the present study was to elucidate the pathophysiology of the liver in adult hypopituitary patients with GHD.

Patients and methods

We recruited 69 consecutive Japanese adult hypopituitary patients with GHD and examined the prevalence of NAFLD by ultrasonography and nonalcoholic steatohepatitis (NASH) by liver biopsy. Patients had been given routine replacement therapy except for GH. We compared these patients with healthy age-, gender-, and BMI-matched controls. We further analyzed the effect of GH replacement therapy on liver function, inflammation and fibrotic markers, and histological changes.


The prevalence of NAFLD in hypopituitary patients with GHD was significantly higher than in controls (77 vs 12%, P<0.001). Of 16 patients assessed by liver biopsy, 14 (21%) patients were diagnosed with NASH. GH replacement therapy significantly reduced serum liver enzyme concentrations in the patients and improved the histological changes in the liver concomitant with reduction in fibrotic marker concentrations in patients with NASH.


Adult hypopituitary patients with GHD demonstrated a high NAFLD prevalence. The effect of GH replacement therapy suggests that the NAFLD is predominantly attributable to GHD.