The stimulatory effect of albumin on luteinizing hormone-stimulated Leydig cell steroid production depends on its fatty acid content and correlates with conformational changes.
The effects of purified albumin species and albumin fragments (0.2-1% w/v) on short-term (4 h) steroid secretion by immature rat Leydig cells, in the presence of a maximally stimulating dose of luteinizing hormone (LH), were investigated. Human albumin and the peptic fragment (comprising residues 1-387) enhanced pregnenolone production in isolated rat Leydig cells, whereas chicken albumin and the tryptic fragment (comprising residues 198-585) were not active. This stimulatory effect of human albumin and the peptic fragment correlated with the potential of these proteins to undergo a pH-dependent neutral-to-base transition as measured by circular dichroism. The tryptic fragment and chicken albumin did not have the potential to undergo such a transition. The pH-dependent conformational changes of albumin and fragments thereof occurred in parallel with a change in the binding affinity for testosterone and pregnenolone. The fatty acid oleic acid and the drug suramin, only when present in a molar ligand-to-albumin ratio equal to or higher than 2, inhibited the albumin-mediated stimulation of steroid production. These data show that the stimulatory effects of albumin species on LH-induced Leydig cell pregnenolone production depend on their fatty acid content and correlate with the potential of these molecules to undergo conformational changes. It is unknown via which mechanisms albumin exerts its stimulatory effect, but the LH action through the cyclic AMP pathway seems not to be affected.
Melsert
R
R
Department of Endocrinology and Reproduction, Medical Faculty, Erasmus University Rotterdam, The Netherlands.
Bos
O J
OJ
van der Linden
R F
RF
Fischer
M J
MJ
Wilting
J
J
Janssen
L H
LH
Hoogerbrugge
J W
JW
Rommerts
F F
FF
D000818:Animals; D002417:Cattle; D002645:Chickens; D002942:Circular Dichroism; D000242:Cyclic AMP / Q000096:biosynthesis; D005227:Fatty Acids / Q000502:physiology*; D006801:Humans; D007985:Leydig Cells / Q000378:metabolism*; D008024:Ligands; D007986:Luteinizing Hormone / Q000502:physiology; D008297:Male; D009829:Oleic Acids / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology; D011284:Pregnenolone / Q000096:biosynthesis*; D011487:Protein Conformation; D051381:Rats; D011919:Rats, Inbred Strains; D012709:Serum Albumin / Q000737:chemistry / Q000502:physiology*; D013498:Suramin / Q000494:pharmacology
D005227:Fatty Acids; D008024:Ligands; D009829:Oleic Acids; D010446:Peptide Fragments; D012709:Serum Albumin; D013498:Suramin; D011284:Pregnenolone; D007986:Luteinizing Hormone; D000242:Cyclic AMP