A dose of 2.5 g of gamma-hydroxybutyric acid (GHB) was administered intravenously to 6 healthy male volunteers. A significant increase in plasma GH was observed at 30, 45, 60 and 90 min after injection. The plasma prolactin level increased significantly at 45 and 60 min after GHB injection. These responses were not found after the saline vehicle injection in the same subjects. It is conceivable that GHB could modify the release of serotonin from the nerve terminals and then stimulate the release of GH and prolactin.

Bovine glomerular basement membrane (GBM) was isolated and purified according to a modification of Spiro’s method. Rat and bovine tubular basement membranes (TBM) were isolated and purified by sonic disruption or by the method of Carlson et al. Electron microscopic studies on the ultrastructure of GBM and TBM were performed after negative staining with 1% phosphotungstic acid solution, pH 7.3. When negatively stained, GBM and TBM were seen as fragments varying in size. The surface of the membranes showed a characteristic felt-like or spongy appearance. At higher magnification, GBM and TBM showed a fine meshwork composed of strands and pores which three-dimensionally resembled a crystal lattice. Pores were fairly uniform in size and shape. They were round, oval or polygonal in shape. Some of the pores were elongated to form short straight or bent channels. Strands were also uniform in diameter and surrounded a pore or channel. For an average of 50 pores, the long dimension was 3.1 ± 0.6 nm and the short dimension 2.5 ± 0.3 nm in bovine GBM, 3.8 ± 1.2 and 2.5 + 0.7 nm in bovine TBM, and 4.9 ± 1.5 and 2.8 ± 0.6 nm in rat TBM, respectively. The strand was 1.8 ± 0.3 nm in diameter in bovine GBM, 2.5 ± 0.6 nm in bovine TBM and 3.7 ± 0.7 nm in rat TBM for an average of 50 strands. The diameters of the pores were less than or close to the short axis of an albumin molecule. It was concluded that renal GBM and TBM were molecular sieves composed of pores and strands.

The effects of various neurogenic peptides and neurotransmitter substances on the release of ACTH induced by hypothalamic corticotropin releasing factor (HY-CRF) were investigated using monolayer cultured anterior pituitary cells. Test substances were given in combination with 0.05-0.1 hypothalamic extract (HE)/ml, because HE evoked a significant ACTH release and a linear dose response relationship was demonstrated sequentially between 0.0165 HE/ml and 0.5 HE/ml. Relative high doses of lysine-vasopressin showed a slight additive effect on the release of ACTH induced by 0.1 HE/ml. Leu-enkephalin, dopamine, prostaglandin E1 and E2 slightly reduced the release of ACTH induced by HY-CRF, but the inhibitory effect of these substances were not dose-related. Other tested substances including luteinizing hormone releasing hormone, thyrotropin releasing hormone, somatostatin, melanocyte stimulating hormone release inhibiting factor, beta-endorphin, neurotensin, substance P, vasoactive intestinal polypeptide, angiotensin II, norepinephrine, serotonin, acetylcholine, histamine and gamma-amino butyric acid showed neither agonistic nor antagonistic effect on the release of ACTH induced by HY-CRF. These results indicate that the release of ACTH is controlled specifically by HY-CRF and corticosterone, and modified slightly by some other substances such as vasopressin and prostaglandins, and that the effect of most other neurogenic peptides and neurotransmitter substances is negligible or non-physiological at the pituitary level.

Corticotropin-releasing factor (CRF) was bioassayed and arginine vasopressin (AVP) radioimmunoassayed from punched-out hypothalamic nuclei. The highest concentration of CRF was found in the median eminence (ME), followed by the paraventricular nucleus (PVN), supraoptic nucleus (SON), suprachiasmatic nucleus (SCN), arcuate nucleus (ARC), dorsomedial nucleus (DMN) and ventromedial nucleus (VMN). The AVP concentration was in the order of ME, SON, PVN, SCN, ARC, VMN and DMN. Sephadex G-25 gel filtration of the ME extracts showed one peak for AVP and two peaks for CRF. One CRF peak appeared on the void volume (big CRF) and the other (small CRF) was coeluted with AVP. Gel filtration of the PVN and SON extracts showed one peak for AVP but three or four peaks for CRF. The addition of anti-AVP serum (AVP-AS) to pituitary cell cultures reduced the CRF activities of AVP and ME extracts by approximately 80 and 40%, respectively. When the small CRF fraction of ME extracts was treated with AVP-AS on affinity chromatography, the unbound fraction (AVP-free) still showed significant CRF activity. Re-examination of CRF concentration using AVP-AS showed that it was still highest in ME, but was significantly higher in PVN than in SON, SCN and ARC. These results suggest that the PVN is an important nucleus for producing corticotropin-releasing hormone.

A 45-year-old, non-obese female patient with no previous history of insulin administration was found to have extreme insulin resistance and abnormally high plasma immunoreactive insulin in the absence of anti-insulin antibodies in the serum. Clinically, there was no ketonuria. The patient also had evidence of Sjogren's syndrome with several immunologic features including hypergammaglobulinemia, positive antinuclear antibodies, accelerated erythrocyte sedimentation rate and leukopenia. Plasma pancreatic glucagon and C-peptide were elevated, but other endocrinologic abnormalties were not present. In this patient the insulin resistance appeared to be due to anti-insulin receptor antibodies which could be detected even in 1:500 dilution of serum. Immunosuppressive therapy with prednisolone and cyclophosphamide resulted in a decreased level of serum gamma globulin and a concomitant decrease of blood glucose level. After immunosuppressive therapy for eight months, the diabetic syndrome disappeared completely and anti-receptor antibodies in the serum were no longer detectable. Furthermore, insulin sensitivity returned to normal. However, the patient's glucose tolerance deteriorated after the temporary termination of cyclophosphamide treatment and the lowering of prednisolone dosage.