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Recent investigations have furnished a complete analysis of the hemodynamic events accompanying whole-body immersion. About 700 ml of blood are translocated into the intrathoracic circulation, and heart volume increases by 180 +/- 62 ml. These changes are followed by an increase in stroke volume and cardiac output of over 30%. At the same time a reflex reduction of total peripheral resistance and venous tone occurs. Renin and aldosterone activity are reduced while the 17-hydroxycorticosteroid is not affected. Treatment of the subject with DOCA attenuates but does not extinguish the excess sodium excretion of immersion. This finding strengthens the arguments in favor of an unknown factor enhancing sodium excretion. Finally, the relative activation of the three factors that serve volume control, the excretory function of the kidney, capillary filtration pressure, and the thirst mechanism, is discussed.

Cortisol has been shown to be metabolized in the zona glomerulosa of the adrenal gland through the same pathway involving the cytochrome P-450, corticosterone methyl oxidase by which corticosterone is transformed to 18-hydroxycorticosterone and aldosterone. When cortisol is the precursor, 18-hydroxycortisol and 18-oxocortisol are formed. 18-Hydroxycortisol can also be made at a similar rate in the bovine zona fasciculata and reticularis as in the zona glomerulosa. We studied the possibility that the formation of 18-hydroxycortisol in the zona fasciculata and reticularis might be through a different pathway involving initial 18-hydroxylation of 11-deoxycortisol before 11 beta-hydroxylation. Rat adrenal capsules or cores were incubated with 10 micrograms of cortisol or 11-deoxycortisol and the formation of 18-hydroxycortisol was measured by radioimmunoassay. Both capsules and cores transformed 11-deoxycortisol to 18-hydroxycortisol, but cortisol was only transformed in the capsular portion. Sixty-two rat adrenals were incubated with 10 mg of 11-deoxycortisol and the putative steroid, 18-hydroxy-11-deoxycortisol, was purified by TLC and HPLC and subjected to gas chromatography mass spectrometry. The mass spectra indicated that the steroid isolated was indeed 18-hydroxy-11-deoxycortisol. The function of this steroid is still unknown.

In manned space flights the renal function and water-salt metabolism undergo substantial changes. With the reserve capabilities of kidneys in mind, their function and regulation of the water-salt balance were investigated in cosmonauts postflight and in Earth-bound simulation experiments with the aid of water loading, hormonal injections (pituitrin, engiotensin, DOCA, ACTH); water- and ion-release were also studied during LBNP and physical exercises. The cosmonauts who performed space flights of 2 to 5 days showed water retention and increased urine excretion of salts during the first postflight days in response to a water load. After the 18-day flight water excretion remained unchanged whereas salt excretion increased. The capacity for osmotic concentration and urine dilution did not alter. The study of the hormonal effect in simulation experiments of different duration demonstrated a normal renal response to the hormonal excretion. After the LBNP tests and physical exercises the water- and salt-excretion declined; a correlation between the level of water- and salt-excretion and the level of these loads was established. The data on the blood- and urine-ionic composition, excretion of nitrogen metabolites, and hormones postflight as well as the results of load and functional tests suggest that changes in the renal function of cosmonauts in weightlessness are associated with regulatory effects on the kidney rather than disturbances in the function of nephron cells.

A highly specific technique based on gas chromatography-mass spectrometry associated with stable isotope dilution was applied to the analysis of follicular fluid aspirated from preovulatory follicles of women under ovarian stimulation prior to in vitro fertilization. Deoxycorticosterone, 21-hydroxypregnenolone and 11-deoxycortisol have been identified and quantified in the nanomolar concentration range. Significant positive correlations were found between these 21-hydroxy-steroids and their immediate precursors, thus indicating a probable common cellular origin. Corticosterone was tentatively identified and cortisol was evidenced at concentrations lower than peripheral plasma levels. The occurrence in human follicular fluid of cortisol, together with different high concentration intermediates, constitutes evidence for ovarian intra-follicular 21-hydroxylase activity, and probably also for 11 beta-hydroxylation enzyme activity.

Microbial transformation by a Bacillus species was employed for the preparation of potentially important derivatives of 11-deoxycortisol. Each microbial metabolite was characterised by the application of various spectroscopic methods. The five metabolites of 11-deoxycortisol were characterised as 4-androstene-3,17-dione (2), 14-hydroxy-4-androstene-3,17-dione (3), 14,17 alpha,21-trihydroxy-4-pregnene-3,20-dione (4), 6 beta,17 alpha,21-trihydroxy-4-pregnene-3,20-dione (5) and 15 alpha,17 alpha,21-trihydroxy-4-pregnene-3,20-dione (6). The availability of the metabolites enabled complete elucidation of their [13C]NMR spectra.

A woman with periodic catatonia had a 600-day metabolic study. The results were analyzed by harmonic analysis. Her periodic stupors showed a regular 36-day rhythm apparently related to a 24-day menstrual cycle; but the rhythm persisted when menstrual function was blocked by continuous Enovid (norethynodrel + mestranol) administration. During the menstrual block, weight, sodium balance, magnesium and 17-ketosteroid (17-KS) excretion gave indications of 12- and 36-day fluctuations. Further studies on steriod excretion indicated that similar fuctuations in 17-KS output occurred when the patient was menstruating normally. The peaks of the 12-day cycle coincided with menses and the mid-menstrual phase; while the peak of the 36-day cycle coincided with the onset of stupor. 17-hydroxycorticosteroid (17-OHCS) excretion had a 36-day cycle which lagged 4 days behind the 36-day 17-KS cycle. There were no indications of a 12-day 17-OHCS cycle. In the discussion it is suggested that the 17-KS fluctuations may partly reflect gonadotrophin activity rather than being exclusively due to ACTH. It is noted that Enovid may block only LH activity not total gonadotrophins. It is speculated that there may be a relationship between gonadotrophin activity and the psychic disturbance.