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The present study was conducted to examine roles of brain monoamines and opioid peptides in growth hormone (GH) secretion in unanesthetized, freely behaving rats. The administration of chlorpromazine (CPZ, 300 microgram/100 g, i.v.), an antagonist of brain monoamines, to rats that were passively immunized with antiserum to somatostatin immediately lowered plasma GH levels and inhibited episodic GH secretion. An intraventricular injection of beta-endorphin (3.5 microgram) stimulated GH secretion. This effect was completely inhibited by the prior administration of naloxone (100 microgram/100 g, i.v.), a specific antagonist of opioid peptides, but not by CPZ. In addition, the administration of naloxone did not inhibit episodic GH secretion. The results suggest that CPZ inhibits episodic GH secretion via a factor(s) other than somatostatin. It is also inferred that brain monoamines, but not opioid peptides, play major roles in the regulation of episodic GH secretion in rats.

Corticotropin-releasing factor (CRF)-like activity in two different kinds of ACTH-producing tumors (human ectopic ACTH-producing colonic cancer and rat MtT/F4 tumor) was determined by an in vitro method using isolated normal rat pituitary cells. The ACTH content of the post mortem colonic cancer was 5.5 ng/g w.wt. The ACTH content of the medium of MtT/F4 tumor cells was 153+/-32 pg/10(5) cells. The ACTH content of MtT/F4 tumor cell suspensions was elevated with increasing doses of hypothalamic median eminence extract (HME). The response of MtT/F4 tumor cells to HME was suppressed by 1 mug/ml of dexamethasone. Extracts of colonic cancer, MtT/F4 tumor and HME produced elevation of the ACTH content of the medium of isolated rat pituitary cells. The CRF-like activities of two kinds of tumor extracts in multiple dilutions ran parallel to that of HME. The CRF-like activities were 0.037 HME equiv/mg w.wt in MtT/F4 tumor and 0.052 HME equiv/mg w.wt. in colonic cancer. These results demonstrated that CRF-like activity existed in these two kinds of ACTH-producing tumors.

Using RIA technique, response patterns of ACTH-adrenocortical system to short term large dose corticosteroid therapy for neurosurgical patients were investigated. The subjects were consisted of 20 males and 13 females, ageing ranging from 10 to 60 years old. The subjects were divided into three groups according to mode of steroid administration. In the first group, 12 mg/day of betamethasone were administered for 5 days and cancelled without gradual reduction. In the second group, 12 mg/day of betamethasone were administered for 4 days and 6 mg/day of betamethasone were given for following 2 days. In the third group, 12 mg/day of betamethasone were administered for 3 days and gradual reduction of betamethasone was given for following 4-5 days. Response of plasma cortisol level to synthetic 18-ACTH were measured in all patients for 3 days after betamethasone administration cancelled. The results led to the following conclusion. 1) The second and third groups had not any clinical symptom after steroid cancelled, but one half cases of the first group had mild headache, nausea for 2 days after cancelled. 2) Recovery process of adrenocortical function in the second group is most rapidly, compared with that in other two groups. 3) In the postoperative steroid therapy in neurosurgery, it could be concluded that 4 days massive administration of steroid followed by stepwise reduction in 2 days would be functionally well tolerated by adrenocortical system.

Basal levels of sex steroids, and the responses of LH and FSH to LH-RH were studied in twenty-five female patients with Cushing's syndrome (17 Cushing's disease and 8 adrenocortical adenoma). Only two patients had a regular menstrual cycle. Amenorrhea or oligomenorrhea had been of long duration in the other cases except for three postmenopausal patients. In patients with Cushing's disease, basal estradiol was low or below normal in 86%. Progesterone was normal in 83%, but testosterone was high in half of the cases. The response of LH to LH-RH in patients with Cushing's disease was normal in 35%, low in 35% and high in 29% of the cases. FSH response to LH-RH was normal in 23.5%, low in 23.5% and high in 53%. In patients with adrenocortical adenoma, basal of estradiol was low or below normal, but progesterone and testosterone were normal in all cases. The response of LH and FSH to LH-RH in all patients with adrenocortical adenoma was higher than normal. In three postmenopausal women, a higher response of LH and FSH to LH-RH was seen in two cases and suppressed in one case. These data suggest that the main site of suppression of the gonadal axis in patients with adrenocortical adenoma is the gonad rather than the pituitary gland or hypothalamus, though the mechanism of hypogonadism in patients with Cushing's disease is heterogeneous.

Pituitary adenomas obtained from 6 patients with acromegaly and 8 patients with chromophobe adenoma were subjected to the tissue culture to correlate in vitro secretion of growth hormone (GH) and prolactin (PRL) to preoperative in vivo endocrine studies and endocrinilogical manifestations. Tissue culture demonstrated that all of the acromegalic tumors secreted large amounts of GH for 2-4 weeks and some of the PRL-secreting chromophobe adenoma without any clinical and endocrinological evidences of GH secretion secreted considerable amounts of GH; however, no recognizable GH secretion was noted in the remaining chromophobe adenomas. PRL was secreted in vitro in large amounts by tumors obtained from patients with hyperprolactinemia with and without acromegaly. It is interesting to note that tumors obtained from 2 patients who showed very slight elevation of plasma PRL of less than 40 ng/ml secreted large amounts of PRL in vitro. This finding suggests that PRL-secreting adenoma could not be ruled out in patients with mild hyperprolactinemia. The duration of in vitro PRL release was longer than that of GH and its rate of decrease was slower than that of GH.

We have studied the clinical usefulness of the CA15-3 radioimmunoassay (RIA) kit that has been developed with two monoclonal antibodies (115D 8 and DF 3). Serum levels of CA15-3 exceeding the normal level were found in a high percentage of patients with ovarian cancer (80%), lung cancer (62.5%) and breast cancer (29.3%). In patients with breast cancer, the mean concentrations of CA15-3 before operation were higher than those after operation. Further, the levels of CA15-3 showed a good correlation with the extent and the stage of the breast cancer. These results suggest that CA15-3 levels can provide monitoring information in the follow-up management of patients with breast cancer.

Effects of CB-154 therapy on the glucose tolerance, IRI and GH responses to the oral glucose administration in 5 acromegalic patients with impaired glucose tolerance were examined. Glucose tolerance improved in all patients with a reduction in GH levels. Insulin secretion in response to the oral glucose administration was exaggerated in 3 patients, while it was supressed in 2 patients who had severely impaired glucose tolerance. After receiving CB-154 therapy, hyperresponsiveness of insulin observed in the 3 patients and a suppressed response in one patient were corrected to normal, while a low response in another stayed unchanged. This observation suggest that variable abnormalities in insulin secretion induced by the excess of GH improve with a decrease in plasma GH levels. However, the abnormal GH secretion in response to hyperglycemia persisted still after administration of CB-154 in spite of decreased basal plasma GH levels.

ACTH, beta-lipotropin (beta-LPH) and beta-endorphin concentrations were determined in pituitary adenomas of the patients with Cushing's disease. Immunoreactive ACTH and beta-endorphin were present in high concentrations and essentially equimolar amounts in pituitary adenomas. beta-LPH conversion to beta-endorphin was activated in pituitaries associated with ACTH/beta-LPH producing adenomas. Immunoreactive ACTH and beta-endorphin concentrations were markedly suppressed in the surrounding tissues.

We have performed tissue culture of pituitary adenomas (5 acromegalies, 7 non-acromegalies) and measured GH, PRL, LH and FSH in the media of tissue culture by radioimmunoassay (RIA) for 30-40 days. In addition, GH, PRL, LH and FSH were measured in the plasma and tumor tissue by RIA. GH concentration in the culture media was markedly high in all cases with acromegaly and high also in 2 out of 7 non-acromegaly cases (case 6 and 7). GH concentration in the media rapidly decreased almost as a straight line on a semilogarithmic scale until the 30-40 in day, when GH level became less than 10 ng/ml. PRL concentration in the culture media was high in 5 patients (3 acromegalies, 2 non-acromegalies). PRL concentration regressed more slowly than GH, but still remained higher than 10 ng/ml in all of the patients on the 25-40th day when the studies were discontinued. LH and FSH concentrations in the culture media was high in two patients. One patient was a pituitary adenoma secreting LH and FSH, and another case was a false high secreting one, possibly contaminated with gonadotropin in normal pituitary gland at surgical operation. LH and FSH concentrations rapidly decreased as that of GH. A rare case of primary LH and FSH secreting pituitary adenoma was demonstrated.

A female case of precocious puberty associated with HCG-producing ectopic pinealoma was reported. The patient, a 5-year-old girl, was referred to the hospital because of headache and choked discs. Physical examination revealed normal physical growth with breast enlargement. Endocrinological study revealed a high plasma HCG concentration of 1192 ng/ml with a normal FSH level. None of HCG, LH and FSH did respond to the LH-RH test. A partial resection of the tumor and an external X-ray irradiation relieved the symptoms and breast enlargement subsided with a remarkable decrease in the plasma HCG level. Histological examination revealed two-cell-pattern pinealoma and electron microscopic findings showed abundant secretory granules in the dark cells. HCG content in the tumor was as high was 400 ng/mg of acetone dried tumor tissue, but no FSH was detectable. Hitherto, all of the reported cases of precocious puberty associated with pineal tumors have been exclusively boys. A normal level of plasma FSH concentration with a somewhat elevated prolactin level might be a contributory factor for the development of precocial sexual development in the present case.

Carcinoembryonic antigen (CEA) levels in the serum and colon tissue were evaluated in 83 patients with colon cancer. The mean concentration of serum CEA increased in parallel with Dukes' stages. CEA concentrations in the cancerous and normal colon overlapped. In the same patient, however, CEA of cancerous colon tissue was always higher than that of normal colon tissue. There was no difference in CEA concentrations in colon cancer between Dukes' A and B. However, in patients with Dukes' C stage, the concentration was higher than in those with Dukes' A and B. The detection of tissue CEA concentration as well as serum CEA is a useful marker for monitoring patients with colon cancer.

To investigate hypothalamic-pituitary functions and the primary site of the lesion in idiopathic pituitary dwarfism, various pituitary function tests, especially the pituitary hormone responses to the hypophysiotropic hormones were studied in 23 patients with idiopathic pituitary dwarfism. A few cases showed slight responses of GH to GH stimulation tests. Gonadotropin deficiencies were most frequently noted among pituitary hormones. The basal levels and the responses of plasma LH and FSH to LH-RH test were diminished markedly in all of the cases except in 5 cases with isolated GH deficiency. Responses of LH and FSH to LH-RH improved markedly after a long term administration of LH-RH for a period of one month in 2 patients with gonadotropin deficiency. As to TSH axis, half of the cases accompanied hypothyroidism. However, the responses of TSH to TRH were normal in all of the cases regardless of the thyroid function. The basal levels and the responses of plasma cortisol and 11-deoxycortisol to the rapid metopirone test were also impaired in about half of the cases. Basal levels of plasma prolactin were normal in all of the cases and the responses of prolactin to TRH were normal in cases with normal thyroid function, but slightly delayed in cases with hypothyroidism. It is concluded from the above observations that the incidences of various pituitary hormone deficiencies were quite high in this disorder and hypophysiotropic hormone deficiencies may cause pituitary hormone deficiencies. Therefore, it is suggested that the primary site of the lesion in this disorder might be at the hypothalamus.

In the rat pituitary gland, immunoreactive angiotensin II (ANG II), renin, and LH, but not PRL, were found within the same cells of the anterior pituitary gland by staining with the avidin-biotin complex method in adjacent sections. No renin-positive staining was observed in the pituitary of the rats after 10 days of castration, but positive staining reappeared after 8 weeks. This effect of castration on renin immunoreactivity was abolished by the simultaneous administration of testosterone. In contrast, ANG II immunoreactivity was unaffected by castration. The intensity of renin immunoreactivity in the pituitary was less prominent in the female than in the male rat. These results suggest that there exists a pituitary renin-angiotensin system localized in the gonadotrophs and that the pituitary renin is under androgenic control.

The placental secretion of Prl, ACTH and immunoreactive (IR)-beta-endorphin were examined in early and later pregnancy with a perfusion method and by determining tissue concentrations of these hormones. Prl was secreted mainly from decidual tissue during 5-6 h long perfusions. Tissue concentrations of Prl were also significantly higher in decidual than in trophoblastic tissue. In contrast, the tissue concentrations of hCG, hPL, ACTH and IR-beta-endorphin were significantly higher in decidual than in trophoblastic tissues. In contrast, the tissue concentrations of hCG, hPL, ACTH and IR-beta-endorphin were significantly higher in trophoblastic than in decidual tissues. Production of hCG and hPL was predominantly demonstrated in trophoblastic tissues by the perfusion method but ACTH and IR-beta-endorphin were too low to be detected by perfusion.

Pituitary adenomas were obtained from eight of nine patients with Cushing's disease, and the surrounding tissues as well were obtained from six of nine patients. ACTH, beta-lipotropin (beta-LPH), beta-endorphin, GH, TSH, LH, and PRL concentrations in these tissues were determined by RIA. Immunoreactive ACTH and beta-endorphin (beta-endorphin + beta-LPH) were present in high concentrations in all adenomas, and low concentrations were found in the surrounding tissues, except for one patient. As compared to levels seen in normal pituitary tissue, the GH concentration in the surrounding tissues was suppressed in five of six cases. TSH and LH concentrations were suppressed in four and three cases, respectively. The PRL concentration was not suppressed in any of the six patients studied. These four hormones were not detected in any adenoma. Plasma GH, TSH, and LH responses to various stimuli which were suppressed preoperatively returned to normal in most of the patients after adenomectomy. Basal plasma cortisol concentrations were normal or subnormal and were suppressed by the administration of 1 mg dexamethasone after adenomectomy, in contrast to the lack of such suppression preoperatively. ACTH and beta-endorphin secretion were stimulated by lysine-8-vasopressin and suppressed by dexamethasone and cyproheptadine in vitro.

The effect of hypophysectomy on the hypothalamic somatostatin content was examined in rats. Somatostatin content in the acid extract of the pituitary stalk and the median eminence tissue (SME) was measured by specific radioimmunoassay. In young male rats, the mean somatostatin content in SME was 63.9+/-5.0 ng. Two weeks after hypophysectomy, it was reduced significantly to 34.4+/-3.3 ng. The result may indicate that the elimination of feedback actions of GH and/or TSH on the hypothalamus led to the decreased synthesis and/or the release of somatostatin. However, the possibility that structural changes in the pituitary stalk and the median eminence tissue ensued after hypophysectomy resulted in the depletion of somatostatin cannot be ruled out.

Immunoreactive (IR)-beta-endorphin, ACTH and cortisol from the plasma of 88 pregnant women during gestation, and 28 women with spontaneous labor were measured. The concentrations of ACTH, IR-beta-endorphin and cortisol gradually increased during gestation. There were significant correlation between ACTH and IR-beta-endorphin (r = 0.79, p less than 0.0001), as well as between ACTH and cortisol (r = 0.54, p less than 0.0001) during gestation. Maternal ACTH and IR-beta-endorphin concentrations rapidly increased during the course of labor, peaked immediately after delivery at 671.3 +/- 136.1 and 513.9 +/- 85.5 pg/ml, respectively, and then decreased two hours later. There was a highly significant correlation (r = 0.89, p less than 0.0001) between ACTH and IR-beta-endorphin during labor. The levels of cortisol were elevated during labor and showed no difference during labor, or two hours later. However, there was no significant relationship between ACTH and cortisol (r = 0.24) during labor. Chromatographic analysis was performed on the pooled plasma extracts from pregnant women at the various stage of labor. In ACTH analysis, a single peak was seen at the position of native ACTH in each case. All detectable immunoreactivities eluted in two peaks at the position of beta-LPH and beta-endorphin. However, beta-LPH to beta-endorphin ratio was almost the same in each case. These results suggest that 1) ACTH and IR-beta-endorphin are secreted concomitantly, probably by the maternal pituitary gland during gestation as well as in response to the stress of labor; 2) the lack of correlation between ACTH and cortisol is due to the difference in metabolic clearance rate of these hormones during labor; 3) neither peripheral nor intrapituitary conversion of beta-LPH to beta-endorphin is seen during gestation and labor.

An ovarian perifusion technique was used to determine if there is a direct suppressive effect of PRL on human gonadal steroid secretion. Ovarian tissue from nine patients was examined. Ovine PRL (0.1-10 IU/ml) directly suppressed progesterone and 17 beta-estradiol secretion by human ovaries. hCG (1-10 IU/ml) stimulated both progesterone and 17 beta-estradiol secretion. Simultaneous administration of PRL (5-10 IU/ml) suppressed the stimulatory effect of hCG. The ovarian tissue obtained from a hyperprolactinemic patient did not respond to hCG. These results indicate that PRL inhibits both basal and gonadotropin-stimulated ovarian steroid secretion by human ovaries and that this may be one cause of the hypogonadism associated with hyperprolactinemia.

We studied the suppressibility of cortisol secretion in 15 patients with Cushing's disease by measuring morning plasma cortisol level as well as the 24-hour urinary free corisol (UFC) excretion following single doses of increasing amounts of dexamethasone (ranging from 0.5 to 32 mg) given at 11 p.m. The mean plasma cortisol level in patients with Cushing's disease was twice as high as in normal subjects, whereas the mean UFC in these patients was 6 times as high. Plasma cortisol in seven patients were suppressed by less than 4 mg of dexamethasone (in 2 cases, less than 0.5 mg; in 3 cases, less than 2 mg; and in 2 cases less than 4 mg). In these cases, basal plasma cortisol and UFC were less than 25 micrograms/dl and 350 micrograms/day, respectively. Among the other eight patients, plasma cortisol was partially suppressed in 5 cases and not suppressed in 3 cases by high doses of dexamethasone (16-32 mg). In these cases the basal plasma cortisol and UFC were more than 25 micrograms/dl and 350 micrograms/day, respectively. There was a significant correlation between the basal plasma cortisol and UFC (r = 0.687, p less than 0.01). These data suggest that the suppression by increasing amounts of dexamethasone in most cases with Cushing's disease was related to the severity of hypercortisolism.

Effects of chlorpromazine (CPZ) on plasma GH and prolactin levels were observed in conscious rats provided with chronic indwelling right atrial cannulae. The administration of CPZ (200 micrograms/100 g b.w. iv) suppressed episodic plasma GH burst and resulted in significant elevations of plasma prolactin levels. These were also observed in rats in which two types of hypothalamic deafferentation, i.e. anterior and complete, had been carried out. The data suggest that CPZ acts within the medial basal hypothalamus and inhibits episodic plasma GH secretion. In addition, it is inferred that catecholamines are involved in the generation of episodic plasma GH burst.

Plasma TSH and prolactin (PRL) responses to insulin-induced hypoglycemia (ITT) were examined in 37 patients with various hypothalamic pituitary disorders. Four patients showed a definite TSH response to ITT. They were 2 patients with suspected pinealoma with diabetes insipidus (DI), a patient with pituitary adenoma and a patient with acute prophyria. A suspected hypothalamic dysfunction and a slightly impaired pituitary function manifested as GH deficiency were their common endocrinological features. On the contrary, plasma PRL response to ITT was noted in about one third of the patients examined, but no concomitant PRL response was observed in any of the patients with a definite TSH response. This suggested a different mechanism of TSH and PRL secretion may be different under this circumstance and a certain factor related to the hypothalamic disorder may play a modulating role in an unusual TSH response to hypoglycemia in these particular patients.

Computed tomography (CT) of the pituitary before and after bromocriptine treatment were performed in 10 patients with microprolactinoma. Intrapituitary low densities were demonstrated in 7 out of the 10 patients before bromocriptine. Low densities shrank in size and increased in density after normalization of the plasma prolactin (Prl) level following bromocriptine. At the same time, various degrees of empty sella were demonstrated in these patients and in 2 out of the 3 without noticeable changes before treatment. It was concluded that enhanced CT scans, especially sagittal reconstruction images, were very informative for the diagnosis of microprolactinoma and that bromocriptine reduced the size of the microprolactinoma and often led to empty sella.

D-Ala, Mephe, Met, enkephalin (Sandoz FK 33-824), 1.0 or 0.5 mg, was administered by i.v. infusion to normal subjects, patients with acromegaly and hyperprolactinemia due to pituitary adenoma and patients with pituitary dwarfism. FK 33-824 induced no significant change in plasma level of LH, FSH or TSH in any of the subjects studied. These results suggest a lesser role of opioid regulation in the release of above pituitary hormones compared with that in GH, PRL and cortisol.

Recombinant human growth hormone is more antigenic than pituitary preparations. Since GH antibodies interfere with radioimmunoassay of GH, we measured plasma free and total GH in patients with pituitary dwarfism with GH antibodies during treatment with a recombinant methionyl GH preparation. Plasma free GH was measured in the supernatant after polyethylene glycol precipitation. Total GH was measured after extracting plasma with acid-ethanol. In normal subjects, both free and total GH levels were similar to those measured in plasma by a direct conventional RIA. Peak free GH levels after administration of 4 IU methionyl GH to 3 normal subjects were 38.0, 30.7 and 13.2 micrograms/1, values similar to those measured in most of the patients with GH antibodies. All values were undetectable in one patient with a very high antibody titre. Total GH levels were similar to free GH levels in normal subjects. In patients with GH antibodies, total GH levels were high compared with their free levels, but similar to those assayed by conventional RIA. The patient with the highest antibody titre had total GH levels which were the lowest of those observed in the patients with GH antibodies in spite of having the highest GH levels measured by conventional RIA. The antibody in this particular case may have a high capacity and a high affinity. A relatively poor growth rate in this patient may be associated with the finding of undetectable free GH levels. Measurement of plasma free and total GH may be of value in examining GH dynamics and their relation to the clinical effectiveness of GH treatment in patients with GH antibodies.

A case is reported in which a human chorionic gonadotropin (HCG-)-producing ectopic pinealoma was found in a 5-year-old girl with precocious puberty. Physical examination revealed abnormal breast enlargement. Endocrinological study disclosed a high plasma HCG concentration of 1192 ng/ml with a normal follicular stimulating hormone (FSH) level. The HCG content of the tumor was as high as 400 ng/mg of acetone dried tissue, but no FSH was detectable. This is the first reported case of precocious puberty associated with pineal tumor in a female.

To investigate the effect of prolactin (PRL) on testicular function, especially on spermatogenesis, testicular inhibin content in male rats treated with PRL was compared with those treated with HMG and testosterone. Mature Wistar male rats were given 10 or 50 IU of ovine PRL, 10 IU of HMG and 5 mg of testosterone, i. m. for 5 consecutive days and testes were removed for assessing inhibin content. Inhibin content was measured by a FSH suppressing activity in cultured rat anterior pituitary cells using aquous extract of testes. Five days' treatment with PRL, HMG, or testosterone did not influence testicular inhibin content in male rats. The possibility that these treatments had transiently affected testicular inhibin content, or that inhibin content did not reflect inhibin production was not ruled out.

To investigate a mode and a site of action of inhibin on FSH and LH secretion, in vivo and in vitro effects of porcine follicular fluid (PFF) on FSH and LH secretion were studied in male rats. PFF administered i.v. suppressed basal FSH levels for 1-8 hr, but did not alter LH levels. On the contrary, PFF given either 1 or 6 hr in advance, suppressed LH-RH stimulated LH responses as well as LH-RH induced FSH responses. In cultured pituitary cells PFF exerted a partial suppressive effect on LH release. PFF suppressed LH release only under the maximal stimulation with 10(-10) M LH-RH and 0.1 mM 3-isobutyl-1-metylxanthine (IBMX) to a lesser degree compared with uniform and greater suppression on FSH release regardless of the experimental conditions. Above results showed a selective suppressive effect of PFF on FSH release and synthesis with a less inhibitory effect on LH release mainly at the pituitary level.

Diagnosis of pheochromocytoma has been made by the determination of urinary noradrenaline and adrenaline excretion for 24 hours. The assay procedure and the collection of urine for 24 hrs. are intricate. In the present study, we have ascertained the clinical significance of urinary normetanephrine (NM) and metanephrine (M), chemically stable metabolites of catecholamines, in single voided urine for a diagnosis of pheochromocytoma. Urine and plasma samples were collected from 361 normal subjects, 59 patients with essential hypertension, 22 patients with chronic renal failure and 22 patients with pheochromocytoma. Urinary NM and M concentrations were determined by radioimmunoassay with prior hydrolysis by acidification with 1N HCl. Plasma NM and M concentrations in normal subjects were 71.8 +/- 30.7 pg/ml and 41.5 +/- 8.61 pg/ml, respectively. Plasma NM was increased in 8 and plasma M was increased in 20 of 21 patients with pheochromocytoma, although many of these overlapped with those patients with chronic renal failure (NM, 285.9 +/- 175.1 pg/ml; M, 206.3 +/- 186.7 pg/ml) and essential hypertension (NM, 107.7 +/- 90.7 pg/ml; M, 46.7 +/- 20.2 pg/ml). Urinary NM and M concentrations did not show specific diurnal variation and there was significant correlations between the values in single voided urine and those in the 24 hour urine. Urinary NM and M concentrations in normal controls were 197.5 +/- 46.7 ng/mg Cr. and 125.3 +/- 37.1 ng/mg Cr., respectively. Urinary NM concentration was increased in 14 and urinary M concentration was increased in all of 17 patients with pheochromocytoma. In addition, urinary M concentration was higher in most of the 17 patients with pheochromocytoma than that in the patients with chronic renal failure and essential hypertension. However, the values in three patients with Sipple's syndrome with a small adrenal tumor or recurrent cases overlapped with those in other diseases. Relationships between urinary concentrations of NM and/or M and tumor size showed positive correlations. Urinary NM and M concentrations showed significant decreases after surgical removal of the tumors. These results suggest that NM and/or M concentrations in single voided urine could be a sensitive and specific diagnostic tool for pheochromocytoma.

D-Ala, Mephe, Met, enkephalin (Sandoz FK 33-824) is a stable long acting analog of methionine-enkephalin. FK 33-824 (0.5 or 1.0 mg), elicited plasma GH and PRL responses in normal subjects. In 23 patients with pituitary dwarfism, the response of plasma GH was markedly impaired, while PRL responded to a variable degree. In patients with acromegaly, there was little or no increase in GH and PRL after FK 33-824. Plasma GH increased to a variable degree after FK 33-824 in patients with hyperprolactinemia, with little change in plasma PRL. FK 33-824 decreased plasma cortisol in normal subjects and patients with pituitary disease. These results show that patients with acromegaly and hyperprolactinemia due to pituitary adenomas and patients with pituitary dwarfism do not respond well to FK 33-824, presumably because of hypothalamic or pituitary derangement.

The effects of testosterone administration on testicular inhibin content and histology were studied in bilaterally cryptorchid rats, in which a marked decrease in testicular inhibin content had been observed. Mature male Wistar rats weighing approximately 300 g were made bilaterally cryptorchid by placing the testes in the abdominal cavity. Testosterone in oil, 0.1, 1.0 or 10 mg, was given i.m. each week. Testicular inhibin and testosterone content, histology and plasma LH, FSH and testosterone were studied 2 weeks later. Abnormally decreased testicular inhibin in cryptorchidism was restored toward normal by testosterone in a dose dependent manner in 2 weeks after surgery. Sertoli cell structure also recovered toward normal with increasing amount of testosterone. Decreased testicular testosterone content and Leydig cell atrophy were observed with suppressed plasma LH and FSH after testosterone. These results showed that the increased plasma concentration of testosterone had a stimulatory effect on the Sertoli cell function in cryptorchidism, in which compensated Leydig cell failure was demonstrated.