Shogo Oki

Presence of immunoreactive beta-endorphin in normal human plasma: a concomitant release of beta-endorphin with adrenocorticotropin after metyrapone administration.

To elucidate whether or not beta-endorphin exists in plasma of normal subjects, plasma extracts obtained before and after metyrapone administration were subjected to gel exclusion chromatography, and fractions obtained were assayed by a sensitive radioimmunoassay for beta-endorphin. The basal plasma level of beta-endorphin was 5.8 +/- 1.1 pg/ml (mean +/- SE, n = 5), which rose significantly to the level of 48.9 +/- 3.8 pg/ml after a single oral dose (30 mg/kg of body wt) of metyrapone administration (P less than 0.001). Plasma ACTH levels also increased from the mean basal level of 73 +/- 4 pg/ml to 269 +/- 41 pg/ml after metyrapone administration. These results indicate that beta-endorphin, distinct from beta-lipotropin, exists in normal human plasma and that it is released from the pituitary concomitantly with ACTH.

Presence of immunoreactive β-lipotropin and β-endorphin in human placenta

Abstract Utilizing a sensitive radioimmunoassay capable of detecting both β-lipotropin (β-LPH) and β-endorphin (β-EP), we demonstrated the existence of immunoreactive β-LPH and β-EP in extracts of human placentas. Gel chromatographic studies revealed that total β-EP immunoreactivity consists of two fractions with elution positions compatible with β-LPH and β-EP, respectively, and a fraction of larger molecular weight. All three fractions showed parallel curves with the standard curve of β-EP in radioimmunoassay. Our observations suggests that β-EP, β-LPH and possibly their precursor exist in human placenta.

Immunoreactive β-Endorphin and Adrenocorticotropin in Human Cerebrospinal Fluid

: To elucidate the significance of beta-endorphin in human cerebrospinal fluid (CSF), CSF levels of beta-endorphin-like immunoreactivity (beta-EP-LI) in various diseases were determined by a specific radioimmunoassay and compared with simultaneously determined ACTH-like immunoreactivity (ACTH-LI) levels in CSF. CSF beta-EP-LI and ACTH-LI in the control group, consisting of 5 normal subjects and 19 patients with nonendocrine diseases, were 22.2+/-1.3 and 14.6+/-0.4 fmol/ml, respectively. CSF levels of these peptides in patients with schizophrenia (n = 19) and acromegaly (n = 10) were not significantly different from those in the control group. Patients with Cushings disease (n = 7) had significantly lower CSF beta-EP-LI and ACTH-LI levels than those in the control group. Four of them showed a parallel increase in CSF beta-EP-LI and CSF ACTH-LI levels after the complete removal of pituitary microadenomas (P < 0.05). Gel chromatography of CSF beta-EP-LI from a normal volunteer, a control patient, and one patient each with catatonia, Nelsons syndrome, Cushings syndrome (adrenal adenoma), and acromegaly gave similar patterns consisting of three peaks with the elution positions comparable to those of authentic beta-endorphin, beta-lipotropin, and possibly their precursor molecule. Gel chromatographic patterns of CSF beta-EP-LI and ACTH-LI were compared in a normal volunteer. The first peaks of beta-EP-LI and ACTH-LI eluted at the same position and the second peak of ACTH-LI coincided with the elution position of authentic ACTH.CSF beta-EP-LI and ACTH-LI levels determined every 5 min over a period of 80 min in three normal volunteers did not show moment-to-moment variability.A significant correlation (r = 0.75, P < 0.001) was seen between CSF beta-EP-LI and ACTH-LI levels in normal subjects and patients studied (n = 73). This suggests that beta-endorphin and ACTH in human CSF share the common regulatory mechanism in normal and pathologic conditions.

Presence of dynorphin-like immunoreactivity in rat pituitary gland and hypothalamus

Using a highly specific and sensitive radioimmunoassay for dynorphin(1-13), dynorphin-like immunoreactivity (dynorphin-LI) was detected in rat pituitary and hypothalamus. Gel chromatographic studies on Sephadex G-50 revealed three components of dynorphin-LI with molecular weights of approximately 7500-9500 (big dynorphin), 3500-5500 (intermediate dynorphin) and 1600-1900 (small dynorphin), the latter of which eluted at the same position as authentic dynorphin contamination in porcine ACTH extracts (Sigma). Dynorphin-LI in rat anterior pituitary existed mainly as big dynorphin, whereas dynorphin-LI in rat intermediate-posterior pituitary and hypothalamus eluted mainly at the position of authentic small dynorphin.

Biosynthesis and distribution of opioid peptides

Group III opioid peptides are derived from proenkephalin B. The processing of this precursor peptide is still only partly understood and we still do not know how many final products come from proenkephalin B and whether Leu-enkephalin is produced from Group III peptides. However, potent biologic activity of Group III opioid peptides and existence of opiate-receptors specific for these peptides (k receptors) strongly suggest that Group III opioid peptides are not precursors of Leu-enkephalin but bioactive substances per se. Further studies should clarify details of the processing of proenkephalin B.

Existence of γ-melanotropin (γ-MSH)-like immunoreactivity in bovine and human pituitary glands

Summary A radioimmunoassay for γ -melanotropin ( γ -MSH) was designed with an antiserum obtained in a rabbit immunized with synthetic γ 3 -MSH. The antiserum cross-reacts with synthetic γ 1 -MSH and γ 2 -MSH and slightly with β -lipotropin, but not with α -MSH, β -MSH, ACTH, and β -endorphin. Using this radioimmunoassay, γ -MSH-like immunoreactivity ( γ -MLI) was detected in bovine and human pituitary glands. Gel chromatographic studies on Bio-Gel P-60 revealed a single component of γ -MLI in the bovine and human anterior pituitary, whereas an additional peak of small γ -MLI was observed in the bovine intermediate lobe.

‘γ-MSH’ fragments from ACTH-β-LPH precursor have an affinity for opiate receptors

Abstract γ-Melanotropin (γ-MSH), a putative peptide residing in the cryptic N-terminal portion of ACTH-β-LPH precursor, shares several amino acid residues with α-MSH or βMSH. The present study revealed that γ-MSH and structurally related peptides had as potent an affinity for rat brain opiate receptors as did ACTH1–24 when 3H-naloxone was used as a ligand. Thus, γ-MSH and structurally related peptides may have physiological significance in the activities of the CNS.

Γ‐MELANOTROPHIN‐LIKE IMMUNOREACTIVITIES IN HUMAN PITUITARIES, ACTH‐PRODUCING PITUITARY ADENOMAS, AND ECTOPIC ACTH‐PRODUCING TUMOURS: EVIDENCE FOR AN ABNORMALITY IN GLYCOSYLATION IN ECTOPIC ACTH‐PRODUCING TUMOURS

Using gel exclusion chromatography on Bio‐Gel P‐60, γ‐melanotropin‐like immunoreactivity (γ‐MSH‐LI) in three human pituitary glands, two ACTH‐producing pituitary adenomas, and three ectopic ACTH‐producing tumours (two medullary thyroid carcinomas and one thymoma) was divided into one or two molecular weight classes. The largest component eluted near the position of mouse 16K fragment and was designated big γ‐MSH‐LI. This big γ‐MSH‐LI was present in all samples. The second one, designated intermediate γ‐MSH‐LI, eluted between the position of mouse 16K fragment and human ACTH, and was demonstrated only in two ectopic ACTH‐producing tumours. No γ‐MSH‐LI emerged at the elution position of synthetic γ3‐MSH.

Liraglutide administration in type 2 diabetic patients who either received no previous treatment or were treated with an oral hypoglycemic agent showed greater efficacy than that in patients switching from insulin

Liraglutide, a glucagon‐like peptide‐1 receptor agonist, is expected to provide a new treatment option for diabetes. However, the suitable timing of liraglutide administration in type 2 diabetic patients has not yet been clarified.

Diabetic ketoacidosis accompanied by hypothermia: A case report

Diabetic ketoacidosis (DKA) is an acute, life-threatening complication of diabetes mellitus and is caused by insulin insufficiency. Hypothermia is defined as a core temperature of less than 35°C and is sometimes accompanied by DKA. We report two patients with diabetes who were admitted for DKA accompanied by hypothermia.