R. Voutilainen*, 0. Ritvos*, V. Ilvesmaki*. A.I. L. Ghizzoni*. R. Virdir, I. Luglia+,O.Hora*, C.Volta*, Kahri*. P. Heikkila* (Introd. by J. Perheentupa). 1 ~e~artmentof ~atholog~,~ediatiics and obstetrics & S. Bernasconi. 16 1 Gynecology. University of Helsinki. SF00290 Helsinki, 164-- - ~eoartmentof Pediatrics. ~niversityof Parma. Italy. 1 Finland. .WU;AI...... COIITICOIROPIN-RELEASIN6.. .. . - .. . .-. FACTO~~.ICRF) . AND ACTH 1 OPPOSITE EFFECT OF PROTEIN KINASE C ACTIVATION ON TEST IN PREMIURE PUBARCHE (PP). STEROIDOGENIC ENZYME GENE EXPRESSION IN HUMAN CHORIO- I Ilerum and plasma concentrations of ~CTH.beta-endorphin (0-E~),dehydroepiandrortcrone CARCINOMA~ ~--~ CELLS AND IN ADRENOCORTICAL CELLS. I The cholesterol side-chain cleavage enzyme (P450scc) is the rate- (~f~).deh~drae~iandrosteronerulfate(OS),17-hydroxyprogesterone (17-oHP),androst limiting and hormonally regulated step in steroid hormone synthe- dione (0 ) and cortisol (F) were aeasured before and after i.v.administration of IugIKg is thought to be the main second messenger sis. Cyclic AMP (CAMP) of CRF (C~FI-41,Nova-0iocehem.CH) in 9 patients with PP (8F,I R. mean age 6.9r1.2yr5, regulating steroid hormone synthesis in all steroid producing or- gans. We studied the effects of 12-0-tetradecanoyl phorbol 13- bone age 7.6t1.3yrs) and in9children with Tanner stages 11-111 (CC)(5F.4 ll,mean age acetate (TPA), an activator of protein kinase C, on P450scc mRNA 11.5rl.2yrs.bone age 11.2tl.5~rs).Thesa.e hormones weremeasured beforeandafter i.v. levels and steroid production in cultured human choriocarcinoma injectionof 0.25.8. ACTH (~~nacten)in the same subjects.The resultrobtained can be s~ (JEG-3), fetal adrenal and adult adrenal cells. In JEG-3 cells marized as fo1lows:CRf test;l)No differences in baseline and peak plasma levels of AClH TPA (up to 100 ng/ml) increased P850scc mRNA accumulation 230 % and 8-EN betucen the 2 groups;2)Peak serum OEA levelsylEA values significantly lover in (p <0.001) and progesterone secrecion 320 % (p <0.01) simultane- PP than in CC(peaks 1.77r0.9v.s.3.12tl.02 ng/ml.p~0.025.xtSO;A0.12t0.47v.s.i.18fO08 ously. In cultured human fetal and adult adrenal cells TPA de- creased ACTH-stimulated P450scc and P450c17 (17-hydroxylase/l7,20 p<0.025);3)Peak 17-OHP serum levels significantly higher inPP compared to CC(1.23iO.24 lyase) mRNA levels 30-80 % (p <0.01). At the same time cortisol v.s.0.81r0.3 ng/ml.p<0.025);4)Peak 0 /peak 17-OHP ratio significantly lower inPP thar and corticosterone secretion decreased at least 50 % (p <0.01). in~~(0.51f0.17v.r.l.26t0.46,p<0.01~.A~TH test:baseline and peak serum levels of all The data show that protein kinase C activation leads to stimu- measured hormones similar in the 2 groups.1n conclusion,different androgen responses to lation of steroidogenesis in choriocarcinoma cells, but to in- CRF administration seem to be inde~endentfrom ACTH and 8-EN secretion.1n PP,under CRF hibition in adrenal cells. Adenylate cyclase activation leads to stimulation,the apparent C -20 lyase activity does not appear to be functioning as in increase in steroidogenesis in both cell types. It will be of in- terest to see if growth factors causing protein kinase C acti- children with the same degr:! OF pubic hair development but with associated gonadarche. vation, will cause similar changes in steroidogenesis as TPA does Yhether this difference inenzyme efficiency is due to the action of a hypothalamic-pi- tuitary factor other than ACTH and B-EN, or to intrinsic adrenal changes is still un-

8. ~.~auffa~*,~.~ol~om~*,~.~.~.~hackleton3~~.~ecsei4 S. Zucchini*, F. Buzi*, A. Lonbardi*. G. Visca*, R. Conti*, P. H. Stoleckel ,J. Homoki5 (introd. by H.Stolecke) Pirazroli. Depts. of Pediatrics,Univ.s of ~ssenland UI~~(FRG], Oepartmentr of Pediatrics. University of Bologna and University of 162 Univ. of ~uda~est(~un~ar~)~.~hi~dren~sHosp.Oakland 165 Brescia, Italy. (USA)), lnst. of Pharmacology ,Univ. Heidelberg(~~~)4 ADRENOCORTICAL INSUFFICIENCY ASSOCIATE0 YITH ACHALASIA AN0 SEVERE HYPOALDOSTERONISM DUE TO CORTICO- STERONE METHYL OXIDASE TYPE II (CMO 11) DEFI- ALACRIRA: VARIABILITY OF CLINICAL FINDINGS IN TYO CASES. CIENCY IN 2 BOYS: METABOLIC AND GAS CHROMATOGRAPHY1 After the 4 patients reported by Allgrave in 1978, only feu carer of the ACTH MASS SPECTROMETRY (GC-MS) STUDIES insensitivity, achalasia and alacrima syndrome have been described. Sone Infection-triggered life-threatening salt loss and hyperkalemia developed in 2 male infants with dystrophy, inappropiately low clinical aspects of the disorder and its pathogenesis has not yet been plasma aldosterone concentrations and elevated plasma renin acti- clarified. Ye report 2 more patients to confirm the clinical entity of the vity. Sodium supplementation but not short-term high dose oral syndrome. Care male patient, developed achalasia at age 2.5 yrs (Heller's 9oc-fluorcortisol (FF) did revert hyponatremia in one boy (Pat.A) nyotomy was carried out) and after 1.5 yrs glucocorticoid deficiency ( skin The other boy (Pat.B) is growing normally on a high sodium diet pigmentation, convulsions uith hypoglycaemia): ACTH> 850 pglml, no response to and oral FF (0.1 mgld). Diagnosis of a defective terminal step of aldosterone biosynthesis was confirmed by measuring urinary ex- ACTH test, nornal aldosterone and PRA. Eyes apparently normal, but evidence of cretion of specific mineralocorticoid metabolites: iapaired tear production after Schiller test. Other features: *uscular Pat. CA THB 18-OH-THA THB + a-THB hypotrophy and hypotonia. foot arthopedie abnormalities. No findings in parents. (y;mo) ~9124h pg124 h C-M -Case 2 female with alarrima since birth; at age 3.5 diagnosis of adrenal (nl. range) (nl. ratio) deficiency was nade (weakness, skin pigmentation, convulsions rith hypogly- A 4;9 640 (0-307) 1249(nl.:not detectable) 0.66 (0.26) caemia): ACTH levels ranging from 229 to 427 pglml, undetectable cortisol B 2;7 160 (0-225) 127(nl.:not detectable) 0.44 (0.18-0.22: Unknown rterolds as candidates responslble for the salt loss coulc levels, urinary aldosterone less than normal. She has sligth dysphagia without not be identified by GC-MS. In conclus1on.GC is mandatory in all radiological signs of achalasia. Isolated findings vithin fanily: alacrima in cases of unexplained salt loss in infancy and childhwd.Short-tern maternal grand - mother, elevated ACTH levels in nother's sister. Conclusions: response to exogenous rnineralocorticoids may not be diagnostic in our cases show the clinical variability of this syndrome; the presence of distinguishing pseudohypoaldosteronlsm from defects in mineralo- isolated achalasia, adrenocortical insufficiency or alacrina in a child rarrants corticoid synthesis. (THA: 11-dehydrotetrahydrocorticosterone, evaluation for the other components. ~a-THB: allo-tetrahydrocorticosterone, C-M: cortisol metabolltes)

M. Janati*, B.P. LeHeup*. A. GCrard, J. Williams*. G. Grignon*, H. GCrard* (Introd. by M. Pierson) Department of Cllnleal Blochemlstry, Unlverslty of 163 Laboratoire d8Histologie et Embryologie, Facult6 de 166 Bonn, F.R.Germany. MCdecine, Nancy et INRA, Tours, France. PROTECTIVE EFFECT OF ATRIAL NATRIURETIC ADRENAL RESPONSE DURING THE GRAFT-VERSUS-HOST (GVH) PEPTIDE (ANP) ON CELLS DAMAGED BY HYPOXIA IN AN AVIAN MODEL OR OXYGEN RADICALS. I The GVH is a frequent camplication of bone marrow transplantation (8111) leading to a multi organ i~aune-mediated pathology. Its endocrine effects are difficlt to analyze in human pathology as BMT requires multiple regimen preparation frequently including radiotherapy. An avian model has been develop- ped to more precisely investigate the endocrine co.plications of GVH. GVH was elicited on 9-day old chicken embryos by adult hista compatible spleen graft an the charia allantoic meabrane. The intensity af GVH was evaluated by the alteration of the embryo spleen. Adrenals from control and allografted animals mere perifused (Endotronicr. USA) during 2 hours and fractions collected every 10 minuter. In the controls, corticosterone production was constant during the perifusion period. llaxinal corticosterone response occurs within 10-20 minutes after the injection of 1-24 ACIH. Ihc optimal ACTH dose war 0.5 uglal. The adrenals of GVH animals shown basal secretion (6.0 + 2.2 ng/m1/100 ngllO mn) similar to the control. The maximal response to ACTH was constantly delayed (peak at the 20-30 minutes fraction) and significantly reduced compared to the control (COO X vr 900 X of the basal values). Ihe present data favor adrenal resistance to ACTH. Such a resirtanre has been previausly found in the thyroid on the same model. The exact mechanisas of this is presently under closer investigation.