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Rice prolamins, a group of seed storage proteins, are synthesized on the rough endoplasmic reticulum (ER) and form type I protein bodies (PB-Is) in endosperm cells. Rice prolamins are encoded by a multigene family. In this study, the spatial accumulation patterns of various prolamin species in rice endosperm cells were investigated to determine the mechanism of formation of the internal structure of PB-Is. Immunofluorescence microscopic analysis of mature endosperm cells showed that the 10 kDa prolamin is mainly localized in the core of the PB-Is, the 13b prolamin is localized in the inner layer surrounding the core and the outermost layer, and the 13a and 16 kDa prolamins are localized in the middle layer. Real-time RT-PCR analysis showed that expression of the mRNA for 10 kDa prolamin precedes expression of 13a, 13b-1 and 16 kDa prolamin in the developing stages. mRNA expression for 13b-2 prolamin occurred after that of the other prolamin species. Immunoelectron microscopy of developing seeds showed that the 10 kDa prolamin polypeptide initially accumulates in the ER, and then 13b, 13a, 16 kDa and 13b prolamins are stacked in layers within the ER. Studies with transgenic rice seeds expressing prolamin-GFP fusion proteins under the control of native and constitutive promoters indicated that the temporal expression pattern of prolamin genes influenced the localization of prolamin proteins within the PB-Is. These findings indicate that the control of gene expression of prolamin species contributes to the internal structure of PB-Is.

Corticosteroids are often used in the treatment of acute viral encephalitis, although the efficacy of corticosteroid therapy has not been proven. We examined the effects of high-dose corticosteroid therapy on acute viral encephalitis in 5 patients with progressive disturbances of consciousness. In 3 patients who were treated within 5 days after the onset of illness, pulse therapy dramatically reduced the degree of consciousness disturbance. They became alert within 24 h, and then neurological symptoms gradually improved. Corticosteroid therapy in the other 2 patients, in whom treatment was started more than 3 weeks after the onset of illness, was not as effective, but repeated therapy at 2-week intervals resulted in complete recovery. These findings suggest that high-dose corticosteroid therapy is effective, particularly for disturbances of consciousness, an important prognostic factor in acute viral encephalitis.

The objective of this study was to evaluate occlusal condition by assessing brain activity in the prefrontal cortex, which is associated with emotion. Functional near-infrared spectroscopy (fNIRS) was used to detect changes in cerebral blood flow in the prefrontal cortex of 12 healthy volunteers. The malocclusion model was a custom-made splint that forced the mandible into retrusion. A splint with no modification was used as a control. The cortical activation during clenching was compared between the retrusive position condition and the control condition. A visual analog scale score for discomfort was also obtained during clenching and used to evaluate the interaction between fNIRS data and psychiatric changes. Activation of the prefrontal cortex was significantly greater during clenching in the mandibular retrusive condition than during clenching in the control condition. Furthermore, Spearman rank-correlation coefficient revealed a parallel relation between prefrontal cortex activation and visual analog scale score for discomfort. These results indicate that fNIRS can be used to objectively evaluate the occlusal condition by evaluating activity in the prefrontal cortex.

The relation of the physiological releases of growth hormone-releasing hormone (GHRH) and growth hormone (GH) into the circulation in various conditions was investigated using a sensitive and specific radioimmunoassay for plasma GHRH. The mean fasting plasma level of immunoreactive (IR)-GHRH in 72 normal adults was 10.3 +/- 0.5 (mean +/- SEM) pg/ml and there was no significant sex difference in the level. The concentrations of IR-GHRH in plasma from the umbilical artery and umbilical vein were 107.3 +/- 20.5 pg/ml and 33.6 +/- 3.8 pg/ml, respectively, and a marked arterio-venous gradient was observed in all 12 individuals examined. The plasma level of IR-GHRH in the maternal vein was significantly lower than that in the cord blood, but was similar to that in non-pregnant women. In normal adults, although there was no apparent fluctuation in the level of plasma IR-GHRH or of plasma GH during bed rest, a significant increase of plasma IR-GHRH was detected followed by, or synchronized with the surge of plasma GH after oral administration of L-dopa. In contrast, on L-arginine infusion, no proportional elevation of plasma IR-GHRH with increase in plasma GH was observed. During and after intravenous infusion of somatostatin, the circulating IR-GHRH level did not increase, but on stopping the infusion there was an immediate and marked rebound surge of GH. We conclude that 1) the elevated IR-GHRH in the cord blood plasma originates from the fetus and may have a primary role in enhancing secretion of GH which promotes growth in early human life, and 2) the participations of GHRH in the mechanisms of GH secretion seen after administrations of L-dopa, L-arginine and somatostatin are different.

Rice prolamins, a group of seed storage proteins, are synthesized on the rough endoplasmic reticulum (ER) and form type I protein bodies (PB-Is) in endosperm cells. Rice prolamins are encoded by a multigene family. In this study, the spatial accumulation patterns of various prolamin species in rice endosperm cells were investigated to determine the mechanism of formation of the internal structure of PB-Is. Immunofluorescence microscopic analysis of mature endosperm cells showed that the 10 kDa prolamin is mainly localized in the core of the PB-Is, the 13b prolamin is localized in the inner layer surrounding the core and the outermost layer, and the 13a and 16 kDa prolamins are localized in the middle layer. Real-time RT-PCR analysis showed that expression of the mRNA for 10 kDa prolamin precedes expression of 13a, 13b-1 and 16 kDa prolamin in the developing stages. mRNA expression for 13b-2 prolamin occurred after that of the other prolamin species. Immunoelectron microscopy of developing seeds showed that the 10 kDa prolamin polypeptide initially accumulates in the ER, and then 13b, 13a, 16 kDa and 13b prolamins are stacked in layers within the ER. Studies with transgenic rice seeds expressing prolamin-GFP fusion proteins under the control of native and constitutive promoters indicated that the temporal expression pattern of prolamin genes influenced the localization of prolamin proteins within the PB-Is. These findings indicate that the control of gene expression of prolamin species contributes to the internal structure of PB-Is.

Plasma growth hormone (GH) responses to various stimuli were examined in 21 patients with GH-producing pituitary adenomas, classified into three types by the immunohistochemistry of cytokeratin and the glycoprotein hormone alpha-subunit distribution. Seven type 1 adenomas were exclusively composed of cells in which the cytokeratin formed a dot-like pattern; they were chromophobic to hematoxylin and eosin (HE), occasionally positive for GH, and almost completely negative for the alpha-subunit. Thirteen type 2 adenomas were composed of cells with cytokeratin that had a perinuclear distribution; they were eosinophilic to HE, and diffusely positive for both GH and the alpha-subunit. One patient had a type 3 adenoma which had a mixed pattern of intracellular cytokeratin distribution and was chromophobic and eosinophilic to HE. Clinically, type 1 is characterized by earlier onset, larger tumor size, and more frequent aggressive extension. Paradoxical GH responses to TRH and OGTT were seen in 1 of 6 patients (16.7%) of type 1 and 8 of 9 patients (88.9%) of type 2, and 0% of type 1 and 62.5% of type 2, respectively. Type 2 cases showed higher plasma GH response to GH-releasing hormone, and a tendency to greater suppression of plasma GH by bromocriptine compared with type 1. Octreotide acetate administration revealed that the nadir/basal ratio of plasma GH levels was 42.9 +/- 6.6% in type 1 and 13.5 +/- 5.8% in type 2. These results suggest that there is a pathophysiological difference between these two distinct types of GH-producing pituitary adenomas.

A radioimmunoassay (RIA) for growth hormone-releasing hormone (GHRH) using a polyclonal antibody against synthetic GHRH(1-29)-Gly4-Cys-NH2 has been developed. The antiserum (RBM105) showed full cross-reactivity with GHRH-(1-44)NH2, GHRH-(1-40)OH, GHRH-(1-37)OH and GHRH-(3-44)NH2, and probably recognized the region of Ala4 to Lys12 of GHRH. Since the sensitivity of the GHRH RIA was 1.5 pg/tube, the lowest detectable plasma level was 5 ng/l when an extract of 0.3 ml of plasma per tube was used. On gelfiltration chromatography, the GHRH immunoreactivity of normal plasma was eluted in the same position as synthetic GHRH. The plasma GHRH concentration in healthy subjects was 20.5 +/- 6.5 ng/l (mean +/- SD), and in patients with hypothalamic disorders was 17.4 +/- 2.0 ng/l. In contrast, the plasma GHRH level in hemodialysis-dependent, chronic renal failure (CRF-HD) patients (38.7 +/- 13.1 ng/l) was significantly higher than normal. The acromegalic patients were 24.3 +/- 11.9 ng/l, except for one patient with ectopic GHRH syndrome (990 ng/l): his plasma GHRH level reached 7,100 ng/l during operation, and then decreased logarithmically to 70 ng/l after 6 h. Somatostatin at concentrations of 10 and 1,000 nmol/l significantly suppressed (GHRH release) from primary culture cells of the GHRH-producing tumor from 17.3 +/- 0.92 ng/2 x 10(5) cells to 9.98 +/- 3.61 and 4.32 +/- 1.01 ng/2 x 10(5) cells, respectively after 48 h. These data indicate that this GHRH RIA is useful for determining the plasma GHRH concentration in normal and diseased states and also for in vitro studies of GHRH release.

A radioimmunoassay (RIA) for the measurement of activin A, which is identical to erythroid differentiation factor (EDF), has been developed. A specific antiserum against activin A/EDF was raised in rabbits using a mixture of recombinant EDF and polyvinyl pyrrolidone. Of the compounds tested this polyclonal antibody cross-reacted only with bovine inhibin (3.2%) and human TGF-β (4.2%). The least detectable value in this assay was 0.06 ng/tube. The within- and between-assay coefficients of variation at three different concentrations were 3.6–9.8% and 3.4–7.7%, respectively. Using this RIA, immunoreactive activin A/EDF levels in various biological fluids and tissues were examined. The dose-response curves of porcine follicular fluid and ovarian extract were parallel to the standard curve, and porcine follicular fluid contained high activin A/EDF immunoreactivity (1050 ng/ml). On gel chromatography of porcine follicular fluid, the major immunoreactivity was eluted in the same position as authentic activin A/EDF. Human placental extract and amniotic fluid had relatively high immunoreactive activin A/EDF levels (174 ng/g wet wt. and 63.9 ng/ml, respectively), but the dose-response curve of amniotic fluid was not parallel to the standard curve. Among rat tissues, the ovary showed the highest activin A/EDF immunoreactivity (163 ng/g wet wt.) much lower than that of porcine ovary (1020 ng/g wet wt.). Low immunoreactive activin A/EDF levels were detected in most parts of rat brain (8.7–14.2 ng/g wet wt.), except for the pituitary gland (70.0 ng/g wet wt.). The initial plasma half clearance time (t 1 2 ) of exogenous activin A/EDF was 14 min in the rat and the plasma FSH concentration did not change significantly during this period. These results suggests that this RIA system has sufficient sensitivity and specificity to measure activin A/EDF concentrations in biological materials, and that the reproductive tissues are the main sources of activin A/EDF.

The GHRH test and L-dopa test were performed in 12 normal young men (24.1 ± 1.1 years) and 12 normal elderly men (77.8±1.4 years) to investigate age-related changes in secretion of GHRH, GH and IGF-I. The basal plasma levels of GHRH and GH were not significantly different in young and elderly men, but the basal plasma level of IGF-I was higher in the young men (159.0± 11.7 vs 86.7± 11.6 μg/1). The area under the curve for plasma GH in the GHRH test was less in the elderly group (35.1 ±5.9 vs 11.2 ± 2.1 μg · h−1 · 1−1, p−1 · 1−1 (p−1 · 1 (p

The function of the growth hormone-releasing hormone (GHRH)-growth hormone (GH) axis in Cushing's disease was studied by monitoring (a) the GH responses to GHRH loading and L-dopa loading, (b) the GHRH response to L-dopa loading, and (c) the daytime profiles of plasma GH concentration. GH release following GHRH and L-dopa was blunted in patients as compared to that in age-matched control subjects. However, GHRH release following L-dopa was similar in patients and controls. The plasma GH levels in four patients measured every 20 min by a highly sensitive immunoradiometric assay for GH showed pulsatile GH secretion at low levels during the observation period. These results indicate that GHRH release from the hypothalamus is preserved in patients with Cushing's disease, and support the hypothesis that glucocorticoid inhibits GH secretion by altering the hypothalamic somatostatin tone.

Severe hypercalcemia (serum calcium, 4.37-4.84 nmol/L) was found in a 70-yr-old man who had a small cell carcinoma of the lung with multiple metastases. The plasma immunoreactive PTH concentration was markedly elevated, as measured in three different PTH assays [N-terminal PTH, 4,650 ng/L (normal, 230-630); midregion PTH, 13,850 ng/L (normal, 180-560); C-terminal PTH, 9,900 ng/L (normal, less than 1,300)], but at autopsy the parathyroid glands were histologically normal. The PTH concentration of a liver metastasis was 503.5 ng/g wet wt (normal liver, less than 4.2-5.9), and the PTH in the tumor extract eluted at nearly the same position as synthetic human PTH-(1-84) on gel filtration chromatography. Northern blot analysis revealed PTH mRNA in the tumor as a single band of 0.9 kilobase. These results indicate that the ectopic PTH production by the lung cancer was the cause of hypercalcemia in this patient.

Hypothalamic-pituitary function was evaluated in a combination of tests with four hypothalamic releasing hormones (4RHs) and L-dopa in normal subjects and in patients with hypothalamic and/or pituitary disorders. Plasma concentrations of anterior pituitary hormones (GH, ACTH, TSH, PRL, LH and FSH) were measured before and after simultaneous iv administration of GHRH, CRH, TRH and LHRH. In addition, changes in the plasma levels of GHRH and GH were investigated before and after oral administration of L-dopa. Normal subjects showed appreciable responses to both tests. In five patients with hypothalamic disorders, the response of plasma anterior pituitary hormones varied, but plasma GHRH and GH did not respond to L-dopa. Patients with idiopathic and postpartum hypopituitarism showed low response to 4RHs or none at all, but L-dopa evoked a normal GHRH response in 2 of the 4 cases having no GH response. In the patients with hypopituitarism due to resection of a pituitary tumor, the response of anterior pituitary hormones to 4RHs was low, and L-dopa administration induced a normal GHRH and low GH response in 5 out of the 7 cases. After 4RHs administration, the patients with ACTH deficiency syndrome showed different patterns of impaired ACTH secretion, and isolated, combined or limited ACTH reserve. Seven patients with anorexia nervosa showed exaggerated GH, delayed TSH and FSH, low ACTH and LH, that is, normal PRL response to 4RHs, but no response of plasma GHRH or GH to L-dopa, suggesting the presence of hypothalamic dysfunction. These results indicate that the combination of the 4RHs test and L-dopa test is a simple and useful means for evaluating hypothalamic-pituitary function by measuring the response of plasma GHRH and six anterior pituitary hormones in the patients with endocrine disorders.

HCG産生鞍上部胚芽腫により,尿崩症,高Na血症,視床下部性下垂体前葉機能低下症,高プロラクチン血症などの視床下部症候群を呈し,経過中に急性腎不全を合併した14才男性例を報告した. TRH・LHRH・LVP・GHRHによる4者負試験およびinsulin, arginine, L-dopaの各負荷試験を用いて,放射線照射と化学療法による治療前後の視床下部下垂体機能の変化を明らかにした.急性糸球体腎炎に起因すると思われる急性腎不全期には,尿量の減少,クレアチニンクリアランスの低下およびNa血症の改善を認めた.尿崩症に腎不全が合併した症例は未だ報告がなく,尿崩症の場合の尿量も糸球体〓過率によって強く影響をうけることが示された.

The plasma levels of immunoreactive-GHRH in patients with idiopathic pituitary dwarfism and acromegaly were studied in the basal state and during various tests by a sensitive and specific RIA. The fasting plasma GHRH level in 22 patients with idiopathic pituitary dwarfism was 6.3 ± 2.3 ng/l (mean ± sd), which was significantly lower than that in normal children (9.8 ± 2.8 ng/l, N = 21), and eight of them had undetectable concentrations (less than 4.0 ng/l). Little or no response of plasma GHRH to oral administration of L-dopa was observed in 7 of 10 pituitary dwarfs, and 3 of the 7 patients showed a response of plasma GH to iv administration of GHRH (1 μg/kg). These findings suggest that one of the causes of idiopathic pituitary dwarfism is insufficient GHRH release from the hypothalamus. The fasting plasma GHRH level in 14 patients with acromegaly and one patient with gigantism was 8.0 ± 3.9 ng/l, which was slightly lower than that in normal adults (10.4 ± 4.1 ng/l, N = 72). One acromegalic patient with multiple endocrine neoplasia type I had a high level of plasma GHRH (270 ng/l) with no change in response to L-dopa and TRH test. In 3 untreated patients with acromegaly L-dopa did not induce any response of plasma GHRH in spite of inconsistent GH release, and in 4 patients with acromegaly, TRH evoked no response of plasma GHRH in spite of a marked GH release, suggesting that the GH responses are not mediated by hypothalamic GHRH. These findings suggest that the measurement of plasma GHRH in response to L-dopa with a sensitive and specific RIA could be of use in clarifying the pathophysiological role of endogenous GHRH in patients with GH secretion disorders.

The production and secretion of immunoreactive growth hormone-releasing factor (IR-GRF) by pheochromocytomas were examined immunohistochemically and immunochemically. GRF-immunoreactive (GRF-IR) cells were found, although sparsely, in 2 of 13 tumors (Cases 1 and 2), while somatostatin (SRIF)-IR cells and vasoactive intestinal peptide (VIP)-IR cells were found in nine and five tumors, respectively. Concentrations of tissue IR-GRF of 29.8 and 17.2 ng/g wet weight tissue, respectively, were found in two (Cases 1 and 2) of three tumors examined. These three tumors also contained IR-SRIF at 19.5-105.5 ng/g wet weight tissue and IR-VIP at 13.6-24.8 ng/g wet weight tissue. An increased plasma IR-GRF concentration (30.0 pg/ml) was found in a blood sample taken from the inferior vena cava near the adrenal tumor in Case 1. This is the first report that some pheochromocytomas produce GRF and secrete it into the blood circulation.

A well-differentiated neuroendocrine carcinoma of the lung that secreted immunoreactive somatostatin (IR-SRIF) and IR-calcitonin (CT) in a 72-year-old women is described. The plasma concentrations of IR-SRIF (57.5 pg/ml) and IR-CT (340 pg/ml) before operation were significantly higher than the respective normal ranges. After resection of the tumor, the plasma CT level (105 pg/ml) decreased to within the normal range, and the SRIF level (32.7 pg/ml) also decreased, but was still abnormally higher, which suggested the presence of an unidentified remnant of the tumor. Abnormal accumulation of technetium 99m (99mTc) in the lumbar vertebrae was found 6 months after the operation, which indicated a metastatic tumor. The tissue concentrations of IR-SRIF and IR-CT were 103 and 94 ng/g wet weight, respectively, and SRIF-IR tumor cells and CT-IR tumor cells were demonstrated immunohistochemically. On gel-filtration chromatography of the tumor tissue, two peaks of SRIF immunoreactivity were eluted in the positions of synthetic SRIF-28 and SRIF-14, respectively. Conversion of SRIF-28 to SRIF-14 was suggested from results on changes in the two IR-SRIF components during incubation with a crude enzyme preparation extracted from the tumor tissue.

A sensitive and specific radioimmunoassay is described for plasma and urinary levels of [D-Ser(tBu)]6des-Gly-NH2(10) ethylamide (buserelin). No appreciable cross-reaction (less than 0.05%) was observed with LH-RH and its analogs other than buserelin fragments (1.6-45%). The sensitivity was 3 pg per tube. At buserelin concentrations of 125, 250 and 500 pg/ml, the intra- and inter-assay coefficients of variation were 7.9, 10.0 and 10.0%, and 19.0, 7.8 and 6.8% respectively. Recovery of buserelin added to plasma was quantitative (62.5 pg/ml, 101.6%; 125 pg/ml, 76.8% and 250 pg/ml, 63.4%). A dose of 5 micrograms buserelin injected subcutaneously into 5 normal male adults, reached a peak plasma level in 45 min (mean value 119.3 +/- 47.3 pg/ml) and remained detectable for at least 4 h. The half disappearance time was 118.8 +/- 26.0 min. Between 9 and 16% of the administered dose was excreted in the urine within 24 h. Buserelin could also be detected in the plasma after intranasal administration of doses of 150, 300 and 450 micrograms. There was a significant difference in the area under the curve (AUC) for plasma levels after subcutaneous injection of 5 micrograms and intranasal administration of 150 micrograms, but not between the AUC values after the three intranasal doses. These results indicate that this method for radioimmunoassay of buserelin is suitable for analyzing the pharmacokinetics and bioavailability of buserelin in man.

The responses of plasma growth hormone-releasing hormone (GHRH) and growth hormone (GH) to oral administration of L-dopa were studied in normal subjects and patients with various endocrine and metabolic diseases to clarify the pathophysiological role of the GHRH-GH axis. In normal subjects, the plasma GHRH concentration was increased from the basal value of 9.8 +/- 1.4 pg/ml (mean +/- SE) to 34.8 +/- 3.1 pg/ml at 30 approximately 90 min after oral administration of 500 mg L-dopa, followed by a rise of GH release (plasma GH level from less than 1 ng/ml to 21.7 +/- 4.7 ng/ml) in most cases, indicating that L-dopa stimulates GH secretion via hypothalamic GHRH. On L-dopa administration, no apparent increases in both plasma GHRH and GH concentrations were observed in patients with hypothalamic hypopituitarism, whereas GHRH administration induced almost normal GH response. In patients with acromegaly, the plasma levels of GHRH remained stationary after the L-dopa administration and did not correlate with plasma GH levels. In subjects with simple obesity, the responses of plasma GHRH (peak 13.2 +/- 1.2 pg/ml) and GH (peak 4.3 +/- 1.7 ng/ml) to L-dopa were significantly lower than those in normal subjects (p less than 0.01). In patients with primary hypothyroidism, peak levels of plasma GHRH (12.6 +/- 1.3 pg/ml) and GH (2.4 +/- 0.6 ng/ml) were significantly lower than those in normal subjects (p less than 0.01). In patients with non-insulin dependent diabetes mellitus (NIDDM), the responses of GHRH and GH were divided into 2 groups; in the responder the peak values of GHRH and GH were 19.4 +/- 8.6 pg/ml and 12.2 +/- 1.4 ng/ml and in the low or non responder 14.7 +/- 1.5 pg/ml and 2.0 +/- 0.6 ng/ml, respectively. Between both groups, there was a significant difference in the values of fasting blood sugar and HbA1 and mean suffering period. These findings suggest that GH secretion evoked by the L-dopa administration is induced by GHRH released from the hypothalamus, and impairment of GH secretion associated with simple obesity, primary hypothyroidism, or NIDDM may be in part attributed to insufficiency of GHRH release from the hypothalamus, and indicate that L-dopa test is clinically useful for evaluating the ability of intrinsic GHRH release in such diseased states.

A 36-yr-old man with multiple endocrine neoplasia (MEN) type I had an ectopic growth hormone-releasing hormone (GHRH) syndrome due to a GHRH-secreting pancreatic tumor. The immunoreactive (IR)-GHRH concentration in his plasma ranged from 161 to 400 pg/ml (299 +/- 61 pg/ml, mean +/- SD; normal, 10.4 +/- 4.1 pg/ml), and a significant correlation was found between his plasma IR-GHRH and GH (r = 0.622, p less than 0.02). After removal of the pancreatic tumor, the high plasma GH concentration returned to nearly the normal range (42.2 +/- 31.3 to 9.6 +/- 3.8 ng/ml). These changes paralleled the normalization of his plasma IR-GHRH (16.1 +/- 3.8 pg/ml) and some of his symptoms related to acromegaly improved. However, plasma GH (7.7 +/- 1.3 ng/ml) and IGF-I (591 +/- 22 ng/ml) concentrations were high at 12 months after surgery, suggesting adenomatous changes in the pituitary somatotrophs. Before surgery, exogenous GHRH induced a marked increase in plasma GH, and somatostatin and its agonist (SMS201-995) completely suppressed GH secretion, but not IR-GHRH release. No pulsatile secretion of either IR-GHRH or GH was observed during sleep. An apparent increase in the plasma GH concentration was observed in response to administration of TRH, glucose, arginine or insulin, while plasma IR-GHRH did not show any fluctuation. However, these responses of plasma GH were reduced or no longer observed one month and one year after surgery. These results indicate that 1) a moderate increase in circulating GHRH due to ectopic secretion from a pancreatic tumor stimulated GH secretion resulting in acromegaly, and evoked GH responses to various provocative tests indistinguishable from those in patients with classical acromegaly, and 2) the ectopic secretion of GHRH may play an etiological role in the pituitary lesion of this patient with MEN type I.

A growth hormone-releasing hormone (GHRH)-secreting pancreatic tumor in a 36-year-old man, who had typical, familial, multiple endocrine neoplasia (MEN) type I with hyperparathyroidism and acromegaly, is described. The resected tumor, weighing 30 g, showed unusual histological features characterized by a meningioma-like arrangement of crescent-shaped cells and contained many cells that reacted with C-terminal specific antibody to GHRH-44 and a few somatostatin-immunoreactive (IR) and calcitonin-IR cells, but no GH-IR cells. A high concentration of IR-GHRH (9.8-13.2 micrograms/g wet weight tissue) with the full molecular size of GHRH-44 was detected in a tumor extract. Electron immunocytochemical study by the protein A-gold method revealed GHRH-IR granules with a mean diameter of 147 nm. After removal of the tumor, the plasma IR-GHRH level became normal (decreasing from 299 to 16.1 pg/ml) and the plasma IR-GH level also decreased, but still remained slightly high (decreasing from 42.4 to 9.6 ng/ml), suggesting the presence of an adenomatous lesion in the hypophysis.