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Unbound cortisol was assayed in maternal and cord plasma. A method was used in which experimental conditions are carefully selected to approach as closely as possible the in vivo situation. ∗ ∗Robin, P., Predine, J., and Milgrom, E.: J. Clin. Endocrinol. Metab. 46:277, 1978. In maternal plasma at term, the proportion of unbound cortisol (9.7 ± 1.5%) (mean ± SE) was identical to that of normal nonpregnant women (9.7 ± 0.4%). However, the concentration of unbound cortisol was 3-fold higher at term (46.0 ± 5.9 ng/ml) than that in nonpregnant women (14.2 ± 1.0 ng/ml). During labor an increase was observed, and at birth the proportion (and concentration) of unbound cortisol was extremely high varying between 17.0 ± 0.8% (92.3 ± 7.4 ng/ml) and 20.9 ± 1.4% (130.4 ± 17.9 ng/ml) (spontaneous and induced vaginal deliveries, respectively). In cord plasma at term and before labor (fetuses delivered by elective cesarean section), the proportion of unbound cortisol was high (29.1 ± 1.3 %) but its concentration (9.6 ± 1.1 ng/ml) was only slightly lower than that observed in normal adults. Labor had an important stimulatory effect as observed in cases of vaginal delivery after spontaneous labor (proportion of unbound cortisol 35.1 ± 1.2%, concentration of unbound cortisol 15.4 ± 1.35 ng/ml, respectively). No difference was observed between spontaneous and provoked labor since similarly high values of unbound cortisol were found in cord plasma after oxytocin-induced labor followed by vaginal delivery (36.2 ± 1.4% and 23.0 ± 5.2 ng/ml).

The effect of dominant urine odour on plasma levels of testosterone and cortisol was studied in the prosimian primate Microcebus murinus. This species shows a photoperiod-dependent cycle of sexual activity. In particular, mean testosterone levels vary from 15 nmol/l during the annual rest period to 245 nmol/l during the breeding season. When males of this solitary and territorial species are artificially grouped in captivity, they develop a social hierarchy which in turn results in physiological disorders, especially of reproductive function, in non-dominant individuals. Since olfactory behaviours appear to be important in the establishment and maintenance of the social structure, we have tested the effects of dominant odorant signals upon the sexual inhibition observed in male conspecifics. A preliminary experiment showed that a decrease in plasma testosterone concentrations could be induced by dominant scent marks. Furthermore, dominant urine odour alone was found to be sufficient to induce this modification. Plasma cortisol levels also increased in these animals. Conversely, when sexually inhibited males were olfactorily isolated from dominant urine odour, testosterone and cortisol concentrations returned to a normal seasonal level. These effects were observed even in males which had had no previous contact with the dominant urine donor. It is inferred from these results that a pheromone-like process could lead to sexual inhibition in male Microcebus murinus exposed to an odorant urinary signal produced by a dominant individual. Nevertheless, the endocrine response seems to vary according to the seasonal period of the sexual activity cycle which suggests that the social effect described is modulated by other external (e.g. photoperiodic) or internal (e.g. reproductive physiology) factors. J. Endocr. (1984) 102, 143–151

7 alpha- and 7 beta-carboxymethyl-derivatives of 17-hydroxyprogesterone and 11-deoxycortisol have been synthesized. After coupling to bovine serum albumin, they were used to elicit antibodies in rabbits. No major difference in the steroid specificity of the antisera was observed when either 7 alpha- or 7 beta-epimers were used for immunization. In both cases, highly specific antisera were obtained which may possibly be used to assay human plasma 17-hydroxyprogesterone and 11-deoxycortisol without chromatographic purification.

A method for measuring the unbound fraction of plasma cortisol which is suitable for clinical use is described. It is shown that unless some precise experimental conditions are fulfilled, important errors may result when determining the unbound fraction of the hormone. The assay is practical (2 ml of plasma are necessary) and reproducible (coefficient of variation: 2.7% within the same assay and 3.1% in different assays). Unbound cortisol measured at 0800 h in 86 healthy individuals was 9.7 +/- 2.6% (SD) of total cortisol and 15.0 +/- 8.5 ng/ml of plasma (temperature: 37 C). No significant difference was found between men and women or according to age. In most cases, variations of unbound plasma cortisol were more important than the variations of total plasma cortisol. This explains why unbound cortisol was a better discriminator in some pathological conditions. In Cushing's syndrome unbound cortisol was found to be increased on the average 2.9 fold whereas total cortisol was only increased by 53%. Unbound cortisol was especially high (24.7 +/- 3.8% of total cortisol and 78 +/- 18.5 ng/ml of plasma) in Cushing's syndrome due to adrenal carcinoma. In adrenal insufficiency, unbound cortisol averaged 6% of total cortisol and 1.4 ng/ml of plasma.

Plasma testosterone was shown to be a very sensitive index of panhypopituitarism in women. In 18 women, testosterone levels were found to be 0.06 +/- 0.04 ng/ml (mean +/- SD; normal, 0.40 +/- 0.10 ng/ml). In all patients, the values were below 2 SD of testosterone levels found in normal women. Dihydrotestosterone concentrations were similarly modified. Such an important decrease in plasma testosterone was probably due to the additional effect produced by the functional suppression of both sources of testosterone precursors: the adrenals and the ovaries.