Biomedical subjects
Publications and source records attributed to N Ling.
The present study demonstrates that synthetic alpha-MSH given as a 2.5 mg intravenous bolus induces an unequivocal rise in LH and FSH in male subjects but not in female subjects during the low estrogen phase of the cycle.
Fragments of the pituitary adenoma of a patient with Cushing's disease were maintained in defined culture medium. Immunoreactive (IR) ACTH, IR alpha-MSH, IR beta-lipotropin (beta-LPH), IR beta-endorphin, and IR gamma-MSHs secreted from the adenoma were studied with gel permeation chromatography and the respective RIAs. The adenoma secreted roughly equimolar quantities of IR beta-LPH plus IR beta-endorphin, IR gamma 3-MSHs, and IR ACTHs. It also secreted IR alpha-MSH as well as IR gamma 1-MSH, although in a much lower concentration than the above four peptides. The secreted gamma 3-MSH-like peptides were found to be glycosylated. The secretion pattern suggests that this particular adenoma processes the pro-opiomelanocortin molecule in pathways which encompass those of both the pars distalis and the pars intermedia.
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The enkephalins Met-enkephalin and Leu-enkephalin were first isolated from porcine brain by Hughes and co-workers. We have recently isolated from bovine adrenals another enkephalin with the structure Tyr-Gly-Gly-Phe-Met-Arg-Phe, or Met-enkephalin-Arg6-Phe7 (ref. 2). We report here that this new heptapeptide is found in human, rat and bovine striatum in concentrations comparable with or greater than that of Leu-enkephalin. This molecule should not be considered as a mere precursor of Met-enkephalin. A pharmacological study indicates that this naturally occurring enkephalin has similar properties to the two enkephalins characterized earlier.
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Rapid and prolonged analgesia was obtained in all of 14 obstetric patients who received synthetic human beta-endorphin intrathecally at the time of delivery. Normal uterine contractions were maintained and all women were fully conscious and highly cooperative in the delivery process. No depression of respiration rate, cardiovascular or central nervous system was observed in any of the patients. Conditions of the infants evaluated by Apgar scoring were excellent. beta-endorphin must be administered intrathecally because it does not cross the blood-brain barrier; for the same reason, beta-endorphin cannot enter the central nervous system of the fetus as do opiates or other drugs commonly used as anesthetics or analgesics at the time of delivery.
gamma-Melanotropin (gamma-MSH), a putative peptide residing in the cryptic N-terminal portion of ACTH-beta-LPH precursor, shares several amino acid residues with alpha-MSH or beta-MSH. The present study revealed that gamma-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, gamma-MSH and structurally related peptides may have physiological significance in the activities of the CNS.
We have isolated from extracts of ovine hypothalamus two molecules characterized as somatostatin-28 and somatostatin-4-28 (referred to as somatostatin-25). They were reproduced by synthesis. In equimolar ratios and depending upon the experimental conditions, synthetic somatostatin-28 and somatostatin-25 are 3 to 14 times more potent than somatostatin-14 to inhibit the basal in vitro secretion of growth hormone. These results suggest that somatostatin-14 as originally isolated, is a biologically active fragment of a larger molecule of greater specific activity, rather than somatostatin-28 being a precursor of the tetradecapeptide.
Nakanishi et al. have recently characterised the complete sequence of the mRNA isolated from the intermediate lobe of bovine pituitary which codes for the 31,000 molecular weight (31K) precursor protein of corticotropin/beta-lipotropin (ACTH/beta-LPH). The corresponding amino acid sequence translated from this mRNA revealed in the cryptic region of the precursor protein a fragment sharing a common amino acid sequence with the alpha- beta-melanotropins (alpha-MSH, beta-MSH) and thus named gamma-MSH. To study whether this gamma-MSH fragment is also processed and released as a biologically active substance and to ascertain its location in the pituitary and possibly in the brain, we have raised antibodies to the synthetic replicate of gamma 3-MSH (ref. 2). We report here the detection of at least two gamma-MSH-like peptides in the pituitary using these antibodies in a radioimmunoassay (RLA) and, furthermore, evidence that these two peptides are glycosylated.
A synthetic peptide, representing a portion of the 16K (16,000 dalton)-fragment sequence within the pro-adrenocorticotropin/endorphin precursor molecule, potentiates the steroidogenic action of the 1 to 24 portion of adrenocorticotropin [ACTH(1-24)] on the rat adrenal cortex. The peptide has 27 amino acid residues and consists of gamma-melanotropin with a carboxyl terminal extension. It affects both the inner and outer adrenocortical zones of hypophysectomized animals, as evidenced by a synergistic augmentation of corticosterone and aldosterone production, respectively. The peptide can be distinguished from adrenocorticotropin by its activation of cholesterol ester hydrolase and its failure to stimulate cholesterol side-chain cleavage.
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A high-molecular-weight protein with beta-endorphin- and adrenocorticotropin-immunoreactivities was isolated from extracts of human placenta after several purification steps, including immunoadsorption with a well-characterized antiserum raised to beta-endorphin. This protein was identified as the heavy chain of the human immunoglobulin class IgG1. These results have led to the recognition of homologies in the amino acid sequences of these physiologically unrelated molecules. They also suggest caution in accepting immunological competence as the sole criterion of the chemical identity of a ligand.
Profound and long-lasting analgesia (mean duration of pain relief 33.4 h, range 22.5--73.5 h) was produced by intrathecal administration of 3 mg synthetic beta-endorphin in all of 14 patients with intractable pain due to disseminated cancer. No respiratory depression, hypotension, hypothermia, or catatonia was observed.
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