A LESS ACIDIC HUMAN FOLLICLE-STIMULATING-HORMONE PREPARATION INDUCES TISSUE-TYPE PLASMINOGEN-ACTIVATOR ENZYME-ACTIVITY EARLIER THAN A PREDOMINANTLY ACIDIC ANALOG IN PHENOBARBITAL-BLOCKED PRO-ESTROUS RATS

Follicle-stimulating hormone (FSH) exists in multiple molecular forms. In both experimental animals and in humans the production and secreti on of less acidic, short-lived FSH glycoforms significantly increase d uring the peri-ovulatory period. To gain further insights on the physi ological role of these FSH variants, we analysed the ability of two FS H compounds, recombinant FSH (rFSH) and purified FSH from urinary orig in (uFSH), (less acidic and acidic pattern of FSH charge isoform distr ibutors respectively) to induce ovarian tissue-type plasminogen activa tor (tPA) enzyme activity in vivo. FSH produced by Chinese hamster ova ry cells and highly purified uFSH were injected at 15:00 h on the pro- oestrous day into phenobarbital-blocked rats and the ovaries were anal ysed for tPA enzyme activity and tPA mRNA concentrations at different times after FSH injection. Induction of tPA enzyme activity by uFSH an d rFSH showed distinct dynamics depending on the particular preparatio n administered. In animals treated with uFSH, maximum tPA enzyme activ ity 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-tre ated groups and none in phenobarbital-blocked, saline-treated controls ovulated. No significant differences were present in the number of ov a shed by rats treated with uFSH or rFSH and spontaneously ovulating r ats (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.