A less acidic human follicle-stimulating hormone preparation induces tissue-type plasminogen activator enzyme activity earlier than a predominantly acidic analogue in phenobarbital-blocked pro-oestrous rats.
Follicle-stimulating hormone (FSH) exists in multiple molecular forms. In both experimental animals and in humans the production and secretion of less acidic, short-lived FSH glycoforms significantly increase during the peri-ovulatory period. To gain further insights on the physiological role of these FSH variants, we analysed the ability of two FSH compounds, recombinant FSH (rFSH) and purified FSH from urinary origin (uFSH), (less acidic and acidic pattern of FSH charge isoform distributors respectively) to induce ovarian tissue-type plasminogen activator (tPA) enzyme activity in vivo. FSH produced by Chinese hamster ovary cells and highly purified uFSH were injected at 15:00 h on the pro-oestrous day into phenobarbital-blocked rats and the ovaries were analysed for tPA enzyme activity and tPA mRNA concentrations at different times after FSH injection. Induction of tPA enzyme activity by uFSH and rFSH showed distinct dynamics depending on the particular preparation administered. In animals treated with uFSH, maximum tPA enzyme activity was detected at 20:00 h, and maximum tPA mRNA concentrations were detected at 17:00 h. tPA enzyme activity induction by rFSH was at the maximum at 17:00 h, and maximum tPA mRNA concentration was at 16:00 h (P< 0.05 for uFSH versus rFSH). All animals in the uFSH- and rFSH-treated groups and none in phenobarbital-blocked, saline-treated controls ovulated. No significant differences were present in the number of ova shed by rats treated with uFSH or rFSH and spontaneously ovulating rats (10.7+/-1.7, 10.0+/-2.6 and 11.3+/-1.6 respectively). These data indicate that the increased biological activity exhibited by less acidic FSH glycovariants at the target cell level may compensate for the drawback imposed by their relatively short plasma half-life.
Timossi
C
C
Department of Pharmacology, School of Medicine, Universidad Nacional Autónoma de México, Mexico, DF.
Damián-Matsumura
P
P
Dominguez-González
A
A
Ulloa-Aguirre
A
A
D000818:Animals; D006224:Cricetinae; D004789:Enzyme Activation / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D006031:Glycosylation; D006801:Humans; D010053:Ovary / Q000187:drug effects* / Q000502:physiology; D010634:Phenobarbital / Q000494:pharmacology; D011359:Proestrus; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
D018691:Excitatory Amino Acid Antagonists; D011994:Recombinant Proteins; D005640:Follicle Stimulating Hormone; D010959:Tissue Plasminogen Activator; D010634:Phenobarbital