Regulation of Plasma Sex-Steroid-Binding Protein in Adult Cynomolgus Monkeys (Macaca Fascicularis) during Different Reproductive States

Abstract

Levels of the sex-steroid binding protein (mSBP) have been characterized in Cynomolgus monkeys, during different stages of reproduction and under hormonal treatments, by an immunoassay allowing a specific and accurate measurement of the protein itself. Using an antiserum specific for native human SBP, we have determined the mSBP level by electroimmunodiffusion. This method correlates closely with the binding capacity measured by a steady-state polyacrylamide electrophoresis. The levels are lower in males (M = 88 +/- 8.6 nmoles/1, n = 6) than in females in the follicular phase (M = 123 +/- 4.4 nmoles/1, n = 5, p less than 0.001) and in castrated males (M = 172 +/- 13.3 nmoles/1, n = 3, p less than 0.001). During gestation, the SBP level decreases (M = 69 +/- 16.3 nmoles/1, n = 7, in the latter part of pregnancy), but during lactation, it is similar to follicular values. Estrogen treatment fails to increase SBP levels in castrated animals, but the values are reduced by testosterone treatment. Since these results are different from those observed in women, we question the validity of using monkeys as models for understanding the mechanisms controlling the concentration of SBP in human blood.

Effect of 17β-Estradiol and Testosterone Treatment on Sex Steroid Binding Proteins in the Female of the Green Frog Rana esculenta

“…While TBP binding capacity could not be restored by hormonal treatment, EBP binding capacity increased almost to the level of the control group. These results are different from those obtained in mammals, where SSBPs are not affected by castration (von Shoultz and Carlstrom, 1989) and androgens seem to play an inhibitory action on SSBP levels in vivo (Toscano et al, 1992;Koritnik and Marschke, 1986;Kottler et al, 1988;). In the only other lower vertebrate studied so far, the trout, androgens do not affect SSBP plasma levels, a result also confirmed by in vitro observations (Foucher et al, 1991).…”

“…Since SSBP are believed to be mainly synthesized in the liver (Mercier-Bodard et al, 1989), we can hypothesize a testosterone effect through its aromatization to 17β-estradiol. Indeed, estrogens have been reported to increase SSBP in human, heifer and trout (Toscano et al, 1992;Lermite and Terqui, 1991;Foucher et al, 1991), although they have little or not effect in monkeys (Koritnk and Marschke, 1986;Kottler et al, 1988).…”

Effect of testosterone on regulation of the level of sex steroid-binding protein mRNA in monkey (Macaca fascicularis) liver

“…(mean = 35 + 3.6 nM over 4 weeks) (Kottler et al 1988), the SBP mRNA increased to the initial level (89%) and the plasma concentration of SBP de¬ creased to the initial value (97%).…”

“…Kottier, Counis & Degrelle (1989) have also demonstrated that both human and monkey SBP are synthesized in a cell-free system by liver RNA, making the monkey a valuable model for studying the molecular events in the biosynthesis of SBP. Nevertheless, previous reports have shown that the hormonal regulation of human and monkey SBP biosynthesis is different: testosterone reduces the plasma levels of both proteins but oestradiol enhances only human SBP levels (Koritnik & Marschke, 1986;Kottler, Tardivel-Lacombe, Domingo et al 1988). Sequence analysis of the human SBP gene has failed to reveal the presence of possible regulatory elements for steroids (Ham¬ mond, Underhill, Rykse & Smith, 1989).…”

“…The Lannoy, France), with a second injection 15 days later. Blood samples (5 ml) were collected by venipuncture before tissue removal, and assayed for SBP and testosterone as previously described (Kottler et al 1988). Monkey hepatic fragments were obtained by surgical biopsy under ketamine anaes¬ thesia.…”