VEGF, VEGF165b and EG-VEGF expression is specifically related with hormone profile in pituitary adenomas.

Vascular endothelial growth factor (VEGF), its inhibitory splice variant, VEGF165b and Endocrine Gland derived VEGF (EG-VEGF) have a controversial role in pituitary gland. We aim to study VEGF, VEGF165b and EG-VEGF expression in pituitary adenomas. A significant correlation was found between growth hormone (GH) and VEGF secretion (P=0.024). For prolactinomas, VEGF and prolactin expression, had a P-value of 0.02 for Kendall coefficient and a P-value of 0.043 for the Spearman coefficient. VEGF-mRNA amplification was detected in both tumor cells and folliculostellate cells. VEGF165b was positive in 16.66% of pituitary adenomas. EG-VEGF was significantly correlated with prolactin (P=0.025) and luteinizing hormone (P=0.028). Our data strongly support VEGF, VEGF165b and EG-VEGF as important players of pituitary adenomas tumorigenesis. Particular hormonal milieu heterogeneity, special vascular network with an unusual reactivity to tumor growth correlated with variability of VEGF, VEGF165b and EG-VEGF secretion may stratify pituitary adenomas in several molecular groups with a direct impact on therapy and prognosis.

Expresión de MLH1, MSH2 y MSH6 en oncocitomas ycarcinomas de células cromófobas renales / MLH1, MSH2 and MSH6 expression in renal oncocytomas and chromophobe cell carcinomas

Objetivos: La alteraciones de los genes reparadores deADN llevan a la inestabilidad de microsatélites y caracterizanal adenocarcinoma familiar de colon no asociado a poliposisy al resto de tumores que se han descrito asociados aeste síndrome. Asimismo, aunque se han visto alterados enun número variable de casos de cáncer esporádico, han sidomuy raramente evaluados en los carcinomas de células renales.Material y métodos: Se han seleccionado 7 oncocitomasrenales y 7 carcinomas renales de células cromófobasmediante criterios histológicos e inmunohistoquímicos convencionales,para el estudio de los genes reparadores deADN mediante la expresión inmunohistoquímica de las proteínasMLH1, MSH2, y MSH6. Resultados: Existe un predominioclaro del sexo masculino, tanto entre los oncocitomas(2F/5M) como entre los carcinomas (3F/4M), con edadesmedias de presentación de 66,8 y 63,4 añosrespectivamente. Entre los oncocitomas renales se ha detectadopositividad para CK20 (4 casos) y CD15 (4 casos),negatividad para CK7 en todos los casos, y pérdida de laexpresión proteica de MLH1 en 1 caso, de MSH2 en 2casos, y de MSH6 en 1 caso. En los carcinomas de célulascromófobas se ha observado positividad para CK7 y negatividadpara CK20 y CD15 en todos los casos, y pérdida de laexpresión de MSH2 en 2 casos y de MSH6 en 3. Conclusiones:El patrón de expresión de las proteínas MLH1,MSH2 y MSH6 en oncocitomas y en carcinomas renales decélulas cromófobas es similar, apoyando la teoría vigente deun mismo origen para ambas entidades en la nefrona distal (AU)

Objectives: Mismatch repair gene disorders lead tomicrosatellite instability and characterise the nonpolyposishereditary colonic adenocarcinoma syndrome. Aside fromthat, the syndrome includes other carcinomas in differentlocations. Mismatch repair gene mutations have been alsodescribed in some sporadic carcinomas of diverse topographies,but only very occasionally in renal cortical carcinomas.Material and methods: Seven renal oncocytomas and7 chromophobe cell carcinomas have been selected followingconventional histological and immunohistochemicalmethods for the analysis of MLH1, MSH2 and MSH6 proteins.Results: There is a male predominance, both inoncocytomas and in carcinomas, with average ages of presentationof 66.8 and 63.4 years, respectively. Among theoncocytoma group, a positive immunostaining for CK20and CD15 has been seen in 4 cases each. Loss of MLH1expression has been detected in one case, loss of MSH2 in2, and loss of MSH6 in one. Among the chromophobe cellcarcinomas, CK7 was positive and CK20 and CD15 negativein all cases. Loss of MSH2 expression has been observedin 2 cases and loss of MSH6 in 3. Conclusions: The patternof MLH1, MSH2 and MSH6 expression is analogous inrenal oncocytomas and chromophobe cell carcinomas thussupporting the nowadays accepted theory of a similar originin the distal nephron for both pathological entities (AU)

Expression of adrenocorticotropic hormone, prolactin and transcriptional factors in clinically nonfunctioning pituitary adenoma.

We describe here a case of a clinically nonfunctioning pituitary adenoma, but with expression of ACTH and PRL. A 42-year-old woman was referred to our department for further evaluation of pituitary tumor. She had no acromegaloid features, and no typical Cushingoid features. She had no galactorrhea, and had regular menses. GH, IGF-I, LH, FSH, TSH, ACTH and cortisol levels in blood were all within the normal ranges, while PRL levels were mildly elevated. Both ACTH and cortisol levels were adequately increased in response to CRH, and both were suppressed by a small dose of dexamethasone. Plasma ACTH and cortisol levels were decreased at night, suggesting the circadian rhythms for plasma ACTH levels were undisturbed. Based on these findings we did not clinically suspect ACTH-producing tumor, however immunohistochemistry revealed ACTH immunoreactivity in the pituitary adenoma. Therefore, the tumor was considered a silent corticotroph adenoma. PRL was co-expressed in a significant subpopulation of ACTH-immunoreactive tumor cells. Ptx1, Neuro D1, and T pit were densely expressed and Pit-1 was sparsely expressed in the nuclei of adenoma cells. It is therefore possible that a tumor originating in an immature or uncommited adenohypophysial stem cell may later differentiate into different cell types due to a combination of certain specific transcriptional factors.

[A case of GH and TSH secreting pituitary macroadenoma]. / Przypadek makrogruczolaka przysadki wydzielacego hormon wzrostu i tyreotropin.

A case of GH and TSH secreting pituitary macroadenoma is reported. A 45-year-old female presented clinical features of acromegaly (the abnormal growth of the hands and feet, with lower jaw protrusion), diabetes mellitus, hypertension, nodular goiter and hyperthyroidism of unclear origin. NMR pituitary imaging revealed intra and extrasellar tumor. The laboratory examinations showed very high plasma levels of GH and IGF-1 and normal level of TSH coexisting with high plasma levels of free thyroid hormones. Pharmacological pretreatment with somatostatin analogues caused the substantial reduction of GH and TSH plasma levels. Histological and immunohistochemical examination of the tissue obtained at transsphenoidal surgery showed GH and TSH secreting adenoma. The laboratory examinations after surgery showed normal GH and IGF-1 plasma levels and reduced insulin requirement, what indicates radical operation. The very low plasma levels of TSH and free thyroid hormones after surgery and immunohistochemical examination suggest central hyperthyroidism due to TSH secreting pituitary tumor (thyrotropinoma).

Neural transformation in a pituitary corticotroph adenoma.

A pituitary mass was removed by the transsphenoidal approach from a 63-year-old man with the clinical history and laboratory findings characteristic of Cushing's disease with partial hypopituitarism. Histological, immunohistochemical, ultrastructural and immunoelectron microscopic investigation demonstrated a periodic acid-Schiff-positive, adrenocorticotropic hormone (ACTH)-immunoreactive, pituitary corticotroph adenoma with the formation of neural tissue resembling neuropil within the tumor. The neural elements showed immunopositivity for neurofilament protein and ACTH, but were immunonegative for other adenohypophysial hormones and for corticotropin-releasing hormone. Although the molecular mechanism accounting for neural transformation in this corticotroph adenoma remained obscure, based on the clinical, histological and morphological findings it appears that formation of neural tissue most likely indicate a favorable prognosis.

Sarcomatoid renal cell carcinoma with foci of chromophobe carcinoma.

Both chromophobe carcinoma and sarcomatoid carcinoma of the kidney are rare. The former is characterized by a relatively good prognosis, while the latter is a highly aggressive tumor. Coexistence of the two components in one renal tumor, which has been reported only rarely, is therefore paradoxical. Both sarcomatoid and chromophobe renal carcinoma were diagnosed in a 52-year-old woman following nephrectomy and resection of metastases in the right lobe of the liver. She died of the disease two months after the first operation; only the sarcomatoid component of her tumor was seen in the liver metastasis and the recurrent carcinoma. Differences in phenotype, immunophenotype and DNA-ploidy patterns of the two components are reported. The intensive p53 staining observed only in the sarcomatoid area supports the role of the TP53 gene in the transformation of chromophobe renal carcinoma to sarcomatoid carcinoma.

Histopathological analyses of silent pituitary somatotroph adenomas using immunohistochemistry, in situ hybridization and confocal laser scanning microscopic observation.

To characterize the morphological and functional aspects of silent somatotroph adenomas with paradoxical responses of GH in TRH or GnRH provocation tests, which are considered to be a useful strategy for endocrinological identification of silent somatotroph adenomas, we examined three silent somatotroph adenomas histopathologically. The adenomas were investigated by immunohistochemistry, including the highly sensitive catalyzed signal amplification system, the non-radioisotopic in situ hybridization method, and confocal laser scanning microscopy. GH production and GH-immunopositive secretory granules in the adenoma cells were demonstrated histopathologically, and the adenomas were interpreted as being densely granulated somatotroph adenomas. Endocrinological identification of silent somatotroph adenomas in combination with paradoxical responses of GH in TRH or GnRH provocation tests may elucidate the increasing number of silent somatotroph adenomas that have been regarded as mammotroph or clinically inactive adenomas. One should be aware of the differences between the previously reported silent somatotroph adenomas, most of which are sparsely granulated somatotroph adenomas, a somatotroph adenomas with paradoxical and the silent somatotroph adenomas, most of which are sparsely granulated somatotroph adenomas, and the silent somatotroph adenomas with paradoxical responses of GH in TRH or GnRH provocation tests, which are densely granulated somatotroph adenomas.

The role of GRH mediated AC-cAMP system in the pathogenesis of human pituitary GH-secreting adenomas.

OBJECTIVE: To investigate the role of AC-cAMP system in the transmission of the action of the growth hormone releasing hormone (GRH) on growth hormone (GH) release in pituitary GH-secreting adenomas. METHODS: The effects of GRH (10(-7) mol/L) on intracellular cAMP levels and GH release and the effects of AC-cAMP stimulators, cholera toxin (Ct, 50 micrograms/L), forskolin (10(-5) ml/L) and db-cAMP (10(-3) mol/L) on GH secretion were studied in cultured cells of 21 GH-secreting adenomas obtained from operation for acromegalic patients. RESULTS: GRH and Ct failed to stimulate GH secretion in 61.9% (13/21 cases) and 57.1% (12/21 cases) pituitary GH adenoma cell cultures respectively. Forskolin stimulated GH release in 88.9% (8/9 cases), while db-cAMP induced GH secretion in all cases tested (5/5 cases). The intracellular cAMP levels were elevated by GRH in the 4 out of 9 cases of tumor cell cultures, but not in the other 5 cases. According to the GH secretory responses to GRH and Ct, the 21 GH tumors were divided into 4 groups. In group A and B, GRH can stimulate GH release, but Ct has stimulative role only in group A. In group C and D, GRH fails to stimulate GH secretion. However group A can respond to Ct, but group D has no response. CONCLUSIONS: The GH hypersecretion in most acromegalic patients is mainly due to the defects of pituitary adenoma cells, especially the abnormalities of GRH receptor and/or stimulative guanosine protein.

[TSH-secreting fibrous pituitary adenoma showing calcification: a case report].

TSH-secreting pituitary adenoma with calcification and proliferation of the collagen fibers was presented. A 42-year-old man had shown general fatigue and thyroid hypertrophy caused by hyperthyroidism for 3 years. CT and MRI revealed pituitary adenoma with calcification extending into the cavernous sinus and sphenoid sinus. The patient was operated on using the transsphenoidal route twice, but the tumor was not able to be removed totally, partly due to the hardness of the tumor. The tumor in- and around the left cavernous sinus as well as the hardest part of the tumor itself due to the calcification could not be removed. Histopathological examination revealed chromophobe adenoma with proliferation of the collagen fibers. Immunohistological and electronmicroscopic examination demonstrated TSH-secreting adenoma. Postoperatively, thyroid function improved and the patient's symptoms due to hyperthyroidism disappeared.

[A plurihormonal adenoma: a case report].

A case of prolactinoma secreting growth hormone is reported. A 32-year-old woman was admitted to our hospital complaining of galactorrhea, amenorrhea and bitemporal hemianopsia. She showed hyperprolactinemia about 500ng/ml and elevated growth hormone level over 10ng/ml without clinical features of acromegaly. Static perimetry represented typical bitemporal hemianopsia better than kinetic perimetry in the early stage of this pituitary tumor. Her visual acuity was 1.0 on the right and 0.02 on the left. MR images showed the intra-and suprasellar mass lesion compressing the optic nerves especially on the left. Because her visual acuity deteriorated rapidly, trans-sphenoidal tumor resection was carried out twelve days after admission. Total removal was achieved. Postoperative MRI showed that the normal pituitary gland had been preserved. The patient's visual acuity recovered to 1.2 on the right and 0.9 on the left, and bitemporal hemianopsia improved remarkably. Postoperative course was uneventful and hormonal functions were normalized. Histological examination showed that the tumor was chromophobe adnoma. The adnoma cells showed immunopositivity for growth hormone, but not for prolactin. Such absence of prolactin granules within cytoplasm might be due to the difference in antigen produced by the adenomatous gland as compared with that produced by the normal gland. Although hyperprolactinemia is often observed in acromegaly, hypersecretion of growth hormone in prolactinoma as was found in this case is very rare in medical literature.

[GH-secreting pituitary adenomas--correlation between clinical features, growth potential and histopathological studies].

We compared clinical features, including endocrinological and radiological findings, histological features and the proliferative parameters (PCNA, MIB-1 and AgNORs) with immunohistochemical features in growth hormone (GH) secreting pituitary adenomas. 18 cases were divided into two groups based on immunohistochemical intracytoplasmic stainings for cytokeratin: a prominent dot-like pattern (group I, 6 cases) and a diffuse perinuclear pattern (group II, 12 cases). Patients in group I (6 females, m = 37.6 years old) were younger, showed female predominance and had a shorter history of acromegaly compared with patients in group II (7 males, 5 females, m = 44.9 years old). Although the size of the adenomas tend to be larger in group I, no difference was recognized in plasma GH levels between the two groups. Increased serum prolactin (PRL) levels were accompanied more common in group I. Abnormal GH responses to TRH and LHRH injection and GH suppressions to bromocriptine administration were more frequently noted in group II than group I. Surgical approaches were transcranial in most cases of group I and transphenoidal in group II. There was no difference in surgical results as to the correction rate of GH levels between the two groups. Histopathologically, group I adenomas were mostly chromophobic, weakly positive for GH, and were generally negative for PRL and alpha-subunit. On the other hand, group II adenomas were mostly acidophilic, diffusely stained for GH, and were often positive for PRL and alpha-subunit. However, there was no significant difference in proliferating parameters between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Caracterización hormonal de los adenomas hipofisarios no funcionantes / Hormonal characterization of the non fuctioning pituitary adenomas

Se estudiaron 98 pacientes con adenomas no funcionantes, 34 hombres y 64 mujeres, realizando un estudio hormonal en suero para conocer su perfil endocrino. Con tal objeto, se efectuaron determinaciones de hormona folículo estimulante y hormona luteinizante (FSH, LH), prolactina (PRL), estadiol (E2), testosterona (T), cortisol, hormona del crecimiento (GH), hormona adrenocorticotrópica (ACTH), hormona estimulante del tiroides (TSH) y gastrina (Ga) por radioinmunoanálisis. Los resultados mostraron marcado hipergonadotropismo en el 47//de los pacientes, con niveles séricos de FSH y LH muy elevados y un incremento inesperado de la concentración de Ga (Grupo I). En contraste, el resto de los pacientes tuvo concentraciones normales o bajas de gonadotrofinas y Ga (Grupo II). El grupo I mostró una relación inversa entre los niveles de gonadotropinas y esteroides gonadales (E2 o T) con cifras significativamente menores que los valores normales y los encontrados en el Grupo II (<0,00l) en el cual la relación fue lineal positiva. Tambien se observó una relación directa entre la concentración de FSH conTSH (r=0,75) y Ga (r=0,80), probablemente por los neurotransmisores que determinan la secreción de estas hormonas. La TSH al igual que las hormonas tiroideas, tuvo cifras más elevadas en el Grupo I, mientras que los valores de PRL fueron más bajos (P<0,0001). La concentración de GH y ACTH fuer normal en ambos,no obstante,el 33 por ciento de los pacientes del Grupo II presentó hipocortisolismo e hipotiroidismo. La edad promedio de los pacientes analizada por décadas, no fue estadísticmente diferente entre los grupos y no explica las diferencias encontradas, aunque en el Grupo I predominaron las mujeres. En éstas, la elevación de FSH podría estar condicionada por la deficiencia gonadal, acorde a la edad de las pacientes (49,8 9,6 años), sin embargo, algunos valores fueron extraordinariamente elevados y existe la posibilidad de que la hipófisis en condiciones patológicas, como es la forma adenomatosa,pueda producir en forma autónoma,moléculas de LH y FSH alteradas y carentes de actividad biológica, o bien, subunidad O libre, como se ha demostrado en algunos gonadotropomas. Por otra parte, algunos de los casos con TSH elevada podrían considerarse verdaderos TS-Homas, que no suprimen su secreción a pesar de la elevada concentración de hormonas tiroideas. Así, podría decirse que dentro de los no funcionantes, están enmarcados algunos de estos adenomas. Se concluye que, desde el punto de vista hormonal, los adenomas del Grupo II son los verdaderos no funcionantes

Growth hormone-producing pituitary adenomas: correlations between clinical characteristics and morphology.

In this study, we compared the clinical and endocrinological characteristics, neuroimaging findings, surgical outcome, and conventional histological findings (including immunohistochemistry) with the electron microscopic appearance of 31 growth hormone (GH)-producing adenomas. By electron microscopy, these 31 tumors were divided into 23 densely granulated somatotroph adenomas (DG adenomas) and 8 sparsely granulated somatotroph adenomas (SG adenomas). SG adenomas more frequently affected younger women, but no significant correlation was found between the adenoma type and the characteristic signs and symptoms of acromegaly, the incidence of diabetes mellitus or hypertension, or the basal serum GH and insulin-like growth factor I levels. A distinct response of GH to thyrotropin-releasing hormone, bromocriptine, or GH-releasing hormone was significantly more common in patients with DG adenomas than in those with SG adenomas, whereas the incidence of a response to gonadotropin-releasing hormone or oral glucose was not significantly different between the two groups. An analysis of neuroimaging findings and surgical results indicated that SG adenomas were more likely to be macroadenomas with suprasellar extension or invasive tumors and had a lower surgical cure rate. However, postoperative radiotherapy seemed to be similarly effective in both types of adenoma to prevent a tumor recurrence and to reduce postoperative GH basal level in serum. Light microscopy showed that DG adenomas were mainly acidophilic and were immunopositive not only for GH but also for prolactin (43%), the beta subunit of thyroid-stimulating hormone (26%), and the alpha subunit of glycoprotein hormone (87%), whereas SG adenomas were almost all chromophobic and only revealed immunopositivity for GH.(ABSTRACT TRUNCATED AT 250 WORDS)

Parathyroid carcinoma in a patient with non-secretory pituitary tumor: a variant of multiple endocrine neoplasia type-I?

We report a case of pituitary adenoma in association with parathyroid carcinoma as an unusual combination of multiple endocrine neoplasia (MEN). A 48-year-old man had a trans-sphenoidal hypophysectomy and transcranial partial removal of a recurrent pituitary chromophobe adenoma followed by a course of radiotherapy in 1980. Four years later, he developed hypercalcemic crisis from a parathyroid carcinoma with invasion to the adjacent thyroid gland and skeletal muscle. A hemithyroidectomy and resection of the left lower parathyroid gland was performed. Three years later, he had local recurrence and anterior chest wall metastasis accompanied by hypercalcemia. After resection of the remnant and metastatic lesion, eucalcemia was achieved. There was no family history of endocrine tumors. This case illustrates the rare association of a malignant parathyroid tumor and a chromophobe adenoma of the pituitary as a variant of MEN syndrome.

Gonadotrophin secretion in vitro by cells of a pituitary tumour from a patient with multiple endocrine neoplasia type I.

OBJECTIVE: The aim was to investigate the hormone secretory products of a pituitary tumour from a patient with multiple endocrine neoplasia type I (MEN I) utilizing cell culture and immunoassay techniques. DESIGN: Adenoma tissue was enzymically dispersed and established in cell culture. Medium was collected for hormone measurement after 2 days, and also after 24-hour periods during long-term culture. In addition, tissue fixed at surgery was analysed by immunocytochemistry and electron microscopy. PATIENT: The subject was a 59-year-old male with a clinical history characteristic of familial MEN I syndrome. MEASUREMENTS: Pituitary hormones in serum and culture medium were measured by fully characterized radioimmunoassays. RESULTS: Preoperative serum LH and FSH levels were normal, or slightly elevated, and there was a progressively blunted gonadotrophin response to GnRH throughout the 8 years prior to adenomectomy. TRH induced a small, paradoxical increase in serum gonadotrophin levels 2 weeks preoperatively. Post-operative pituitary hormone responses to standard stimulation tests showed an active normal pituitary. In vitro, the pituitary tumour cells secreted only gonadotrophins and glycoprotein hormone alpha-subunit. The fixed tumour tissue immunostained for alpha-subunit alone, and electron microscopy confirmed the presence of secretory granules with diameters of 100-280 nm. Gonadotrophin secretion continued throughout 77 days in long-term culture, but whilst LH was released at a steady rate, that of FSH transiently increased between days 29 and 48 in vitro. CONCLUSIONS: These data demonstrate that a pituitary tumour associated with the MEN I syndrome secreted gonadotrophins in vitro.

[Spheroidal deposits of amyloid in prolactin-secreting pituitary adenomas]. / Depositi sferoidali di amiloide in adenomi ipofisari secernenti prolattina.

Nine peculiar cases of pituitary adenomas were pointed out by a retrospective investigation at the Ospedale di Legnano (from 1978 to 1984) and at the Ospedale di Circolo di Varese (from 1973 to 1986). These tumours are chromophobe adenomas with diffuse structure. Histologically they show typical, large, spheroid and concentric amyloid deposits, in addition to common, amorphous--often perivascular--ones. They were investigated by histochemical methods (Crystal-Violet, Congo-Red) and by immunohistochemical ones as well (anti-PRL and anti-GH), showing that these deposits are amyloid and are in close relation with PRL production. In particular, by immunohistochemical methods we found out that the cells of the tumours displaying spheroidal bodies do contain prolactin, not GH. The amyloid deposits are also immunohistochemically positive to anti-PRL serum, not to anti-GH serum. Finally, by considering the information present in literature, we have discussed the possible pathogenic mechanisms leading to amyloid deposits in pituitary adenomas.

[A case of pituitary adenoma with simultaneous secretion of TSH and GH detected by double immunostaining method].

A rare case of simultaneous hypersecretion of thyroid stimulating hormone (TSH) and growth hormone (GH) in a pituitary adenoma is reported. A 59-year-old male complaining of general fatigue, dyspnea on exertion and finger tremor was admitted. Examination on admission, he revealed with hyperthyroidism and hypersecretion of TSH and thyroid hormones. Administration of TRH did not further increase serum TSH level, and administration of T3 also had no effect on TSH secretion. CT scan showed a pituitary macroadenoma 13mm in diameter. MRI demonstrated a homogenously hypointense mass with Gd-DTPA enhancement in the left side of the sella turcica. The entire chromophobic adenoma was removed by trans-sphenoidal surgery. Immunostaining of the specimen showed that the cytoplasm of the adenoma cells was positive for both TSH and GH. Double immunostaining using avidin-biotin-peroxidase complex (ABC) method and immunogold silver staining (IGSS) method, showed that the adenoma cells had been secreting both GH and TSH at the same time. After the adenomectomy, the hyperthyroidism disappeared, and all altered indicators of pituitary function returned to normal.

Invasiveness of pituitary adenomas.

528 biopsies from 396 pituitary adenomas were re-examined by light microscopy and checked for invasion of neighbouring tissues. The overall invasion rate was 41.9%. Highly differentiated ACTH-cell adenomas were invasive in 24.1%, undifferentiated mucoid-cell adenomas in 66.7%. The histological type of invasion was influenced by the adenoma type and by the invaded tissue. There was no obvious correlation between the adenoma type and the invaded tissue.

[Effect of dopamine and bromocriptine on secretion of growth hormone by pituitary growth hormone secreting tumor in cell culture].

This article reports the effect of dopamine (DA) and its agonist bromocriptine (CB154) on the secretion of growth hormone (GH) by pure GH-secreting pituitary tumor in cell culture as well as a comparison of the effects of these dopaminergic drugs and SMS201-295 (SMS). DA of 10(-8) and 10(-7) mol/L reduced GH secretion to 50.6 and 44.4% of the control, respectively, in 1 out of 6 tumors. CB154 of 10(-7) and 10(-6) mol/L suppressed GH secretion to 59.0 +/- 8.9% of the control in 3 out of 4 tumors. CB154 was at least 10 times less potent than SMS vis a vis GH secretion. CB154 of 10(-6) mol/L inhibited GH secretion to 63.3 +/- 13. 8% (n = 4), but SMS of 10(-7) mol/L induced GH secretion to 45.5 +/- 13.1% (n = 4), the concentration difference between CB154 and SMS was 10 times. CB154 suppressed not only GH secretion, but also GH synthesis in two tumor cell cultures. The major role of SMS in GH secretion was inhibition. The results suggest that DA and CB154 have direct inhibitory effects on GH secretion, at least in some pure pituitary GH secreting tumors. The activities of DA and CB154 are not entirely the same as that of SMS.