The compound 2-methyl-1: 2-bis-(3-pyridyl)-1-propanone (SU 4885) is now widely used in testing the reserve capacity of the pituitary gland to secrete adrenocorticotrophic hormone. In the opinion of Liddle, Estep, Kendall, Jr., Carter Williams, Jr. & Townes (1959) it is a relatively specific inhibitor of 1 1 \ g = b \ -h y d r o x y l a t i o n . This view has been supported by experimental and clinical evidence. For instance, Grant (1960) showed that SU 4885 decreased 1 1 \ g = b \ -h y d r o x y l a s e activity, but left the 17-and 21-hydroxylating enzymes unaffected.Recently, however, results have accumulated that throw doubt on the specific inhibitory action of SU 4885 on 1 1 \ g = b \ -h y d r o x y l a t i o n .Loraine (1962) found that SU 4885 administered in high doses caused a decrease in steroid formation which was greater than inhibition of 1 1 \ g = b \ -h y d r o x y l a t i o n alone could account for. Venning, Lucis, Dyrenfurth & Beck (1962) showed that the drug increased the urinary excretion of pregnandiol. Grant (1960) raised the point that SU 4885 may have a direct stimulatory effect on 11-deoxycortisol formation in the adrenal gland and Ganong & Gold (1960) suggested a direct effect on the hypothalamo-hypophysial system.In the present work, nine healthy women were each given a 24 hr. course of 3-0 g. of SU 4885 (Metopiron, CIBA) administered orally in doses of 500 mg. every 4 hr. Complete 24 hr. collections of urine were made on the day before, during, and on the day after treatment. Urinary oestrogens were determined by the method of Steczek & Koref (1963).The effects of SU 4885 on urinary oestrogen values are summarized in Table 1. All subjects showed marked decreases in oestradiol excretion (P < 0-001), certainly more considerable than could have occurred during the observation period without the drug. The decreases in oestriol and oestrone excretion were less marked in most subjects. Two possibilities can be adduced to explain the decreases in the excretion of oestra¬ diol : decreased oestradiol formation or accelerated oestradiol metabolism. We incline to the view that the former is the more valid explanation. Griffiths (1963) has recently shown that, in addition to producing an inhibitory effect on ll/?-hydroxylase, SU 4885 inhibits 19-hydroxylation. The latter plays a major role in oestradiol forma¬ tion (Longchampt, Gual, Ehrenstein & Dorfman, 1960), for in the steroid ring A hydroxylation at C19 is the first stage in aromatization. It seems likely that, when hydroxylation is inhibited, less A4-androstene-3 :17-dione is converted to oestradiol and that, instead, other ll-deoxy-17-oxosteroids are produced. This concept is sup¬ ported by the observation (Foldes, Koref, Fehér, Steczek & Krasznai, 1963) that a fall in urinary oestradiol is accompanied by increases in both androsterone and aetiocholanolone excretion. The marked effect of SU 4885 raises the interesting possi¬ bility that the compound exerts not only a selective effect on the adrenal cortex but

151According to experimental data calcium ions are involved both in the secretory process (Grodsky and Bennett 1966, Mi/ner and Haies 1967, Malaisse and Malaisse-Lagae 1970_and the action of imulin (Kissebah, Hope-Gill, Vydelingum, Tulloch, Garke and Fraser 1975). Since only a few cJinicai observations have been reported on this subject so far, it seemed worthwhile to investigate the effect of an altered serum calcium on glucose tolerance, blood glucose and IRI levels. Materials and Methods11 diabetics -treated with diet or diet + antidiabetic drugs and 53 non-diabetics were investigated: all the diabetics and 46 of the non-diabetics (normal group) received 10%, caa 2 (3.6 mg Ca++/kg b.w.) intravenously. Blood was taken before and 5,15,30,60, 120 and 180 minutes after the i.v. injection for the determination of serum calcium (Ray Sarkar and Chau· han 1967), glucose (o-toluidin method), IRI (Amersham-KIT, double antibody technique of Haies and Randle 1963), and cortisol (fluorimetric method of Mattingly 1962), 7 of the non-diabetics served as controls: their blood glucose and cortisol were measured without previous calcium load.A self-controlled mathematical analysis was carried out using Student's t test. AU the changes were compared to the initial (zero minute) values and the means were given within the 95% fiducial limits: i( ± t(0.5) . si(' In a further study 50 g oGTT was performed in five hypocalcemic patients (see Table). Three days later the oGTT was repeated with a simultaneous i.v. caa2 injection (3.6 mg Ca++/kg b.w.). Blood sugar and IRI were determined from venous blood sampies at 0, 15, 30, 60 and 120 minutes. IRI

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a need for a prospective study to determine the differential effects of uremia, dialysis and immunosup- Abraham, G.E.: Solid-phase radioimmunoassay for Estradiol-17B. Re[erencesPituitary responsivencess to Luteinizing Hormone-Releasing Hormone in insulin-dependent diabetes mellitus. Diabetes 24: 378-380 (1975a) Distiller, L.A., J.E. Morley, I. Sagei, M. Pokroy, R. Rabkin: Pituitary-gonadal function in chronic renal failure: the effect of luteinizing hormone-releasing hormone and the influence of dialysis. Metabolism 24: 711 720 () 97 5b) Epstein, S., B.L. Pimstone, D. le Roith: Kineties 01' GnRH disappearanee in normal subjeets and in patients with liver and renal disease. S. Afr. Med. Joum. 50: 1004 (1976) Feldman, H.A., I. Singer: Endoerinology and metabolism in uremia and dialysis: A c1inieal review. Medicine 54: 345-369 (l974) Furyama, S., D.M. Mayes, CA. Nugent: A radioimmunoassay for plasma testosterone. Steroids 16' 415 -428 (1970) Goodwin, N.J., e. Valente, J.E. Hall, EA. Friedman: Effeets of uremia and ehronie hemodialysis on the reproduetive eycle. Am. J. Obstet. Gynae 100: 528-535 (1967) Guevara, A., P. Vidt, M.e. Hallberg, E.M. Zom, e. Pohlman: R.G. Wieland: Serum gonadotrophin and testosterone levels in uremie males undergoing intermittent dialysis. Metabolism 18: 1062 1070 () 969) Downloaded by: University of British Columbia. Copyrighted material.Insulin-, Glucagon-and Calcitonin-Induced Early Decrease in Serum Calcium 73 rat calcitonin administration decreased serum calcium significantly, however, at the time intervals employed this early decrease could not be differentiated from the well-known hypocalcaemic effect of this hormone. Both the alterations of blood glucose after insulin and of blood glucose and IRI after glucagon were preceeded by changes in serum calcium. On the analogy of literat ure data about parathormone action, this early hypocalcaemic effect of insulin. glucagon and calcitonin may be due to activation of target ceHs by these hormones.