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R C Pedersen

Publications and source records attributed to R C Pedersen.

28 records · Page 2Linked to original sources
PubMed1983

Cholesterol metabolism in the rat adrenal cortex: acute temporal changes following stress.

Adrenal and serum corticosterone concentrations, cholesterol association with adrenal cortical cytochrome P-450scc (the cytochrome P-450 catalyzing the conversion of cholesterol to pregnenolone), and adrenal cortical activities of cholesteryl ester hydrolase, acyl-CoA:cholesterol acyltransferase, and cholesterol side-chain cleavage have been determined at various times following stress in female rats. The paramount importance of cholesterol side-chain cleavage activation in the response to stress at the low point of the circadian rhythm is confirmed. At the high point of the circadian rhythm, there is evidence that the provision of free cholesterol for the cytochrome P-450scc enzyme system may also be controlled. The data support a coordinate action of ACTH and pro-gamma-melanotropin in controlling cholesterol metabolism in the adrenal cortex following stress.

Adrenal Cortex↗
PubMed1983

Lys-gamma 3-melanotropin binds with high affinity to the rat adrenal cortex.

Partially purified plasma membrane preparations from the inner zones of the rat adrenal exhibit a specific and high affinity for a pro-gamma MSH peptide, synthetic rat Lys-[125I-iodo-Tyr1] gamma 3MSH, that is time and temperature dependent, reversible, and saturable. Studies with demedullated adrenals indicate that at least part of this binding is to the adrenal cortex. Scatchard analysis reveals a single class of binding sites (101 fmol/mg membrane protein) for the radioactive ligand, with an apparent Kd of 0.74 nM. However, this may understate the receptor affinity for native pro-gamma MSH(s), because the binding capacity of Lys-gamma 3MSH is impaired somewhat by iodination. Lys-[125I-iodo-Tyr1] gamma 3MSH exhibits a 100-fold higher affinity for the binding site than ACTH-(1-24), but unlike ACTH, concentrations of Lys-gamma 3MSH up to 10 microM fail to stimulate membrane-associated adenylate cyclase activity. Guanylate cyclase in this subcellular fraction also is unresponsive to Lys-gamma 3MSH. Results obtained with crude membrane fractions from other rat tissues suggest that specific pro-gamma MSH binding may not be unique to the adrenal cortex.

Adenylyl Cyclases↗
PubMed1982

Immunoreactive gamma-melanotropin in rat pituitary and plasma: a partial characterization.

A RIA for the gamma MSH region of proopiomelanocortin has been established and validated. The antiserum was raised to synthetic bovine gamma MSH, and it cross-reacts well with larger polypeptides, including gamma MSH and 16K fragment, which contain the gamma MSH sequence. Gel filtration chromatography of extracts prepared from the anterior and neurointermediate lobes of rat pituitary and from rat plasma reveal two heterogeneous immunoreactive (IR-) forms of gamma MSH in each venue which elute in molecular weight peaks of approximately 11,000 (11K) and 6,000 (6K). Addition experiments indicate that the smaller material is not an artifact generated from the larger form during preparation. By the criterion of retention on affinity columns of Concanavalin A-agarose, these peptides are glycosylated. The 6K form represents 8-17% of the total IR-gamma MSH in the anterior lobe and about 30% of that in the neurointermediate lobe. IR-gamma MSH are released by dispersed rat pituitary cells in response to several of the same secretagogues which modulate the secretion of other proopiomelanocortin-derived peptides. Changes in the plasma and anterior lobe content of IR-gamma MSHs and ACTH resulting from perturbation of the pituitary-adrenal axis are concordant. In particular, the plasma concentration of 6K IR-gamma MSH increases dramatically after imposed stress.

Amino Acid Sequence↗
PubMed1980

Pro-adrenocorticotropin/endorphin-derived peptides: coordinate action on adrenal steroidogenesis.

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.

Adrenal Cortex↗
PubMed1980

Adrenocortical response to corticotropin is potentiated by part of the amino-terminal region of pro-corticotropin/endorphin.

Five peptides derived from pro-corticotropin/endorphin (pro-ACTH/endorphin), the pituitary corticotroph cell prohormone, were bioassayed with isolated rat adrenocortical cells: alpha- and beta-melanotropin, beta-lipotropin, beta-endorphin, and the amino-terminal region of pro-ACTH/endorphin known as "16k fragment." The effect of each on steroidogenesis was measured at potentially physiological concentrations (0.01-1 nM) in both the absence and presence of varying concentrations of ACTH-(1-24). Of the peptides tested, only 16k fragment, the amino-terminal region of pro-ACTH/endorphin, has a slight but significant potentiating effect on ACTH-(1-24) action. Prior treatment of 16k fragment with trypsin for 30 sec dramatically increases this dose-dependent synergism. Experiments performed in vivo with hypophysectomized female rats indicate that the trypsin digest of 16k fragment stimulates cholesterol ester hydrolase (cholesterol esterase; sterol-ester acylhydrolase, EC 3.1.1.13) activity in the adrenal cortex but fails to activate cholesterol side-chain cleavage. The effect of the trypsinized material can therefore be qualitatively distinguished from that of ACTH-(1-24). When both ACTH-(1-24) and the digest are administered together, a synergistic increase in serum corticosterone concentration results. We propose that a portion of 16k fragment molecule may play a hormonal role in the control of adrenocortical steroidogenesis.

Adrenal Cortex↗
PubMed1977

Sensitive, optimized assay for serum AMP deaminase.

A sensitive, optimized assay for serum AMP deaminase (EC 3.5.4.6) is presented, which is based on a colorimetric indophenol determination of ammonia liberated during the enzyme reaction. An average enzyme activity in serum of 2.7 U/liter (n = 36, range 0-6.2) for healthy adults was established. Both the enzyme and colorimetric reactions were optimized to give an assay sensitivity of 0.2 U/liter of serum, a 98-99% analytical recovery in the normal serum enzyme concentration range, and a CV of 7.9% in-run and 10.6% between-run. This optimization included studies on specific buffer, pH, ionic strength, and potential activators. The Km for the enzyme in serum was determinated to be 1.4 X 10(-3) mol/liter, which agrees well with the value reported for human skeletal muscle enzyme. Above-normal serum AMP deaminase activity may be present in various myopathies and could be useful in detecting carriers of the X-linked dystrophies.

AMP Deaminase↗
PubMedDate not supplied

Polypeptide activators of cholesterol side-chain cleavage.

A rate-determining step in the cAMP-dependent action of ACTH on adrenal steroid biosynthesis is the interaction of cholesterol substrate with the cholesterol side-chain cleavage cytochrome P-450 in the mitochondrion. This interaction is rapidly and reversibly sensitive to inhibitors of protein synthesis. For this reason a hormone-dependent, labile protein activator of cholesterol side-chain cleavage has long been postulated as an obligatory intermediate in the tropic regulation of this reaction. Applying recent advances in liquid chromatography, two-dimensional gel electrophoresis, and enzyme reconstitution into liposomes, several laboratories have now reported the isolation and partial characterization of polypeptide candidates for the status of "labile protein."

Adrenal Cortex↗