Sayomi Iida

Growth hormone-producing pituitary adenoma with crystal-like amyloid immunohistochemically positive for growth hormone.

Growth hormone (GH)‐producing pituitary adenoma from a 50‐year‐old acromegalic female was studied histochemically, immunohistochemically and electron microscopically. The adenoma was characterized by numerous crystal‐like amyloid bodies of 5 to 40 μm in diameter. In the periphery of the crystal‐like amyloid, bundles of amyloid fibrils were closely associated with deep invaginations of adenoma cells. The adenoma cells had numerous vesicles and vacuoles filled with amyloid fibrils, some of which were continuous with extracellular space. The crystal‐like amyloids, as well as the adenoma cells, were immunohistochemically positive for GH. It might be possible that disorder of hydrolysis of “prohormone,” from which GH is elaborated, is responsible for the amyloid production, and that amyloid discharge is accompanied with immunoreactive GH.

Forskolin potentiates adrenocorticotropin-induced cyclic AMP production and steroidogenesis in isolated rat adrenal cells.

Forskolin, a unique diterpene which directly activates the adenylate cyclase, stimulated production of both cyclic AMP and corticosterone in isolated rat adrenal cells, in vitro. This agent also potentiated the action of adrenocorticotropin and/or cholera toxin on cyclic AMP production and steroidogenesis at lower concentrations. It augmented both an early (cyclic AMP production) and a late (steroidogenesis) action of the hormone in the adrenal gland.

Familial Renal Hypouricemia with Intact Reabsorption of Uric Acid

Three patients with renal hypouricemia in the same family are described. Serum urate levels in the mother were in the low normal range and were below normal in her 2 sons. In all 3 patients, the ratios of renal urate clearance to creatinine clearance were abnormally elevated. Clear responses to either pyrazinamide or probenecid administration were observed in these ratios. These results suggest that these 3 patients had renal hypouricemia with normal reabsorption of urate as judged by the criteria for differentiating abnormalities in renal urate handling. This corresponds to the previously postulated mechanism as renal urate hypersecretion. Possible limitations to the diagnostic use of probenecid and pyrazinamide are also discussed.

An Enzyme-Linked Immunosorbent Assay (ELISA) For Adenosine 3′, 5′-Cyclic Monophosphate (cAMP) In Human Plasma and Urine Using Monoclonal Antibody

A reliable and sensitive ELISA for cAMP in human plasma and urine is described, using a monoclonal antibody and a 96 well microtiter plate. Succinyl cAMP is conjugated to human serum albumin and adsorbed to the ELISA plate, giving an immobilized antigen approach which simplifies subsequent assay procedures. As low as 1.56 fmol/well of both plasma and urinary cAMP is measurable. Recoveries of added cAMP in plasma and urine were from 99% to 109%. Intra-assay coefficients of variation were less than 6.1% for plasma and 7.0% for urine samples. Inter-assay coefficients of variation for plasma and urine samples were less than 8.9% and 9.5%, respectively. There was a good correlation between the values obtained by ELISA and radioimmunoassay (RIA) (plasma: r = 0.94, n = 66; urine: r = 0.98, n = 64; nephrogenous cAMP: r = 0.96, n = 51).

Presence of ACTH-Potentiating Factors in Rat Anterior Pituitary Glands

High molecular weight ACTH fractions, obtained through gel filtration of boiled rat anterior pituitary extract, induced a marked increase in corticosterone production from isolated rat adrenal cells in the presence of low concentrations of ACTH-(1-24). This indicates the presence of heat-stable factors augmenting the steroidogenic action of ACTH in the rat anterior pituitary. We also noted that these factors potentiated the activity not only of ACTH-1(1-24) but also of ACTH-(1-8). The ACTH-potentiating factors in rat anterior pituitary extract are possibly present in heterogeneous forms according to their molecular weights (8,000, 10,000 and 15,000), their mobility in ion-exchange chromatography and their content in RIA-ACTH activity. Of these three forms, the former comigrated with biological ACTH activity. The remaining two forms were free of it. Since the effect of potentiating factors on modified ACTH-(1-9), shown to be less susceptible to proteolytic degradation from ACTH-(1-24), was similar to the effect on ACTH-(1-24), it is suggested that potentiation was not due to an inhibition of ACTH proteolysis.

UNALTERED STIMULATION OF PITUITARY ADRENOCORTICOTROPHIN SECRETION BY CORTICOTROPHIN‐RELEASING FACTOR FOLLOWING SODIUM VALPROATE ADMINISTRATION IN A PATIENT WITH NELSON'S SYNDROME

A 53‐year‐old woman with Nelsons syndrome was treated with 600 mg sodium valproate daily. Her plasma ACTH was effectively decreased, whilst the response of plasma ACTH to corticotrophin‐releasing factor (CRF) was unaltered. The result of the CRF test suggested that sodium valproate, at least in the present patient, acted at the hypothalamic level.

Steroidogenic effect of ent-kaur-16-en-15β-ol (kaurenol) on isolated rat adrenal cells

In an in vitro bioassay system for adrenocorticotropic hormone using isolated rat adrenal cells, kaurenol, a diterpene alcohol, stimulated corticosterone production and augmented the steroidogenic effect of adrenocorticotropin or forskolin, dose-dependently. Kaurenol had no effect on cyclic AMP production by the cells. The diterpene also had no stimulatory effect on the adrenal adenylate cyclase activity in a cell free system. The results suggest that this particular diterpene exerts a steroidogenic effect through a mechanism independent of cyclic AMP generation.

Partial Characterization of ACTH-Potentiating Factors Derived from Porcine Thymus

We have demonstrated the presence of ACTH-potentiating factors in porcine thymus which contained neither biologically active nor radioimmunoassayable ACTH. The factors were acidic and heat stable in nature, and were present in heterogeneous forms having various molecular weight. Purification of the factors with small molecular weights was performed using reversed-phase high-performance liquid chromatography following gel filtration and cation-exchange chromatography. A purified factor exerted dose-dependent ACTH-potentiating activity. Loss of the ACTH-potentiating activity of purified factors by treatment with carboxypeptidase Y indicated their peptidic nature. ACTH-potentiating activity was readily observable after preincubating the adrenal cells with the thymic extract. The enhancement of ACTH-induced steroidogenesis by the factors was observed in the presence of bacitracin at a concentration to prevent ACTH degradation. Therefore, the existence of potentiating mechanisms other than inhibition of ACTH proteolysis was indicated.

Presence of Adrenocorticotropin-Potentiating Activity in a Calcitonin Preparation Derived from Porcine Thyroid Glands

A calcitonin preparation derived from porcine thyroid glands exhibited potentiating activity on the steroidogenic action not only on ACTH-(1-24) but also of ACTH-(1-18) in isolated rat adrenal cells in vitro. This activity was demonstrated in various molecular weight fractions resulting from gel filtration of the preparation. This preparation also contained minute amount of immunoreactive and biologically active ACTH.

A Case of Weak Mineralocorticoid-Producing Benign Adrenal Tumor

Tumors producing weak mineralocorticoids are exceedingly rare and most of them predominantly produce 11-deoxycorticosterone. We present a case of adrenocortical adenoma in which the overproduction of 18-hydroxydeoxycorticosterone exceeded that of 11-deoxycorticosterone.