E.FrCjavilleX, H.C. Pifferi*, C.Cesarif, S.Partesottix. G.Pagnix.C. N.G.Forest, A.Ltcoqx and PI.David*. IIJSER1:-U. j'l Pediatric Clinic, HGpital Debrousse, Lyon, France. Tramonti*, V.Santi*, L.AbatiX, E.Cacciari 128 25 SEX HCRMONE BIIIDIIANDROGEN SENSITIVITY IN INFANTS AND CHILDREN. gna, Italy. BREAST CONTACT THERNOGRAPHY IN DIFFERENTIAL DIAGNOSIS OF PREMATURE Establishing a reliable test of androgen SfnSlti- THELARCHE AND PRECOCIOUS PUBERTY. vity is still prerequisite for etiological disgnosis in order to contribute to the differential diagnosis between idiopathic in infants suspected of androgen insensitivity syndr20me (.&IS). Premature Thelarche (PT)and true Precocious Puberty (PP) ue performed Breast Since androgens are known to decrehse SBP levels we have invcsti- Contact Thermoaraohv (BCT. cholesteric liouid crystal ~lates)in 13 airls vith PI gated the possibility of using plaslna SBP as a marker of andro~ell A,,. . . . and 12 vith PP (previously diagnosed) and in105 controlgirls (~~~~~~t~ 81.5). ~Cn~itivity,and studied the conditions for a ratlonal protocol. The Ontokenic Of birth was first We evaluated the 4 principal components (Fundus, vascularization, nipple and established in 695 controls, (by a solid phase method). SEP periareolar heat changes). Arbitrary gradual scores (0,I.Z ...) uere attributed to (Ug/l) low at birth, (~-3~3)rise to 22.3t7.5 during the the maturative signs. A Thermographic Index (TI= sum of the 4 scores of a single first montti of life correlatively with time, with no sex diffcren- breast) and the higher TI (hTI= betueen the 2 breasts of single girls) were ce but larbe individual variations. In aodition, SBP decreased

calculated..-~~-~- significantly after either an acute or a ?-day routine ACTH test. Whatever the age (1 mo-13 yr), SBP levels decreased significbntly Results: in controls, single scores, TI and hTI had a positive correlation - (c, (mean=30%) in a group of 40 boys at the end (day 14) of an hCG p <0.001) with B stages. In PI, all signs of vasculariration Mere aluays (100%) test (1500 IU/48 h x 7), but the responsf was very varidble arid absent, while in PP they uere aluays present, although in some cases monolateral- not with testosterone levels. sn cony.ast, the exo- ly. The TI of PI uas not different from 01 girls and significantly louer genous administration of fluoxyrnesterone (10 mg/q /d.x 10 (1.) or (p<0.001) than PP girls and B>1 controls. The hTI ranged from 0 to 3 in PT, from depo-testosterone (4 IM injections of 100 mg/mL every 2 ,decks) 4 to 13 in PP airls. induced a siginificant drop (mean 2 fold) in 10 infants witt, idio- We conclude that lou TI (< 3)and no signs of vascularizationindicate PI, pathic male pseudOhermaphroditism, but not in 2 susl;ected of AIC. In ConclusiOn' SBP appears 'Ood 'larker Of androgen sensitivity vascular hyperthermia and hTI2 4 indicate PP. We emphasize the useful diagnostic in infancy, however establishing a protocol requires thrce aid of the noninvasive imaging technique of BCT in evaluating the pathophysiology conditions: 1) the test should not be done ourlnc the lst month -~ ~-~-~-. of pubertal breast development. of life (rising basal levels), 2) neither after an ACTli test and 3) utilise the exogenous administration of a high dose of androgens for somewhat a prolonged period of time.

L.AU~I*,A. Carrascosa*, D.Yeste* , A. Ballabriga* H.hller*, K.Miller*, B.Cwcke*, A.Attar?dsio,D.Qpta. ( Introd. bv C. Marti-Henneberq ) 129 Lkpt-Diagwstic EnQcriwlcgy,lhiv.Childrtrl's tbspital, Aospital Germans Trias-Pujol & Hospital Infant11 de 74 ~bii@n, FRG. la Val1 d'Hebron,Autonomous University of Barcelona AGE-DEPWNT EFFECTS OF MLATONIN PCMINISTR4TICN CN PROSTATIC S~ain. CYTOSOL AUCGN ECEPTOR5 IN M4LE RATS SPECIFIC ANDROGEN BINDING IN HUMAN FETAL EPIPHYSEAL CHONDRCCYTES IN CULTURE . Human fetal epiphyseal chondrocytes were obtained in primary Chronic daily adninistration of relatonin (MT) can have pterh effects on culture ( Ped. Res. 19:720,1985 ) . In this system testosterone rqm.3xtiffl in the experimtal animals. Various theories have been elaborated (T) was metabolized into androstendione and dihydrotestosterone to explain these "piml" effects on gonads. In the preserh study we have (DHT) ( J. Clin. Endocrinol. Metab. 58:819,1984 ) and we have re- exanired the prostatic cytosol ardrcpn receptor (AR) respnse in pubertal cently shown that DHT significantly stimulates chondrocyte proli- (35-day-old) and adult (70-day-old) mle Wistar rats to doses of 250 &kg b.w. feration . MT (in 0.5 ml saline) adninistered s.c. for 4 days at 17.00 hr each day with In order to study the mechanism of androgen action on human fe 12 h (6.m18.00 h) light per day. The control group received only saline tal epiphyseal cho drocytes , cells have been incubated with DHT- for 4 consecutive days. The animls were sacrificed at 7 a.m. follcwiq the 3H ( 0.1 - 9 x 10-gM ) with and without 200-fold unlabelled DHT last dose. In the pubertal group 6 pls wt of 24 animls the rean cytosol for 30.at 37% . Cells were sonicated in Tris 0.02M-HCl pH=7.5 , PSI declined significantly (p-0.03) fma level of 263120 fnoll~W4 sea 0.5 M KC1 , 1.5 mM EDTA , 2 mM Mercaptoethanol . Unbound DHT was in the control animals to a level of 94.3+119 fml11rg for the MT-treated separated with KCBuffer . Maximal binding capacity and Kd were group. There was also a decline for the c@sol receptors in the adult group calculated according to a Scatchard plot . In chondrocytes from bch the difference did not reach significance. Interestiqly, the studies fetuses ( 20-40 weeks-old ; 4 #and 4 O ) Bmax In fis 4.2 ; 1.2 again ccnfinred that pernaps cytosol AR is wt dependerrt on tesbsterow, fmol/mg Prot. and in 0 5.5 ;0.5 ; Kd 1s 0.34 ;0.14 nM in dand as there was w difference in testostem levels bet- the control and the 0.65 ;0.21 in 9 . ~o+differencewas found for sex nor for gesta- experirmtal gmps. Chronic injections of MT for 4 days in adult bch rat tional age . in ymanimls suppressed circulatitq MT levels Wen sarples were collected Human fetal epiphyseal chondrocytes in primary culture seem 14 h after last irljectim. The current study convinciqly dglanstrates that therefore to present proteins which may act as typlcal specific chmic injections of MT for 4 days in the late light phase of the light- androgen receptors . These results suggest that biological acti- dark cycle have marked inhibitory effeds on the prostatic cytosol AR in the vity of androgens on human fetal epiphyseal chondrocytes in cul- pubertal animls bch wt in the adults as was evidenced earlier in an in- ture may be mediated through specific receptors . direct exprimnt (bller et al. (I=), Res Exp M 183,157-165).

I.A. HUGHES, B.A.J. EVANS? Department of Child 130 M.Muritano*, M.Zachmann, A.Prader 127 Health, University of Wales College of Medicine, Department of Pediatrics, University of Zurich, Cardiff. OK- Switzerland. TRANSIENT OVARIAN TESTOSTERONE AND ANDROSTENEDIONE ANDROGEN INSENSITIVITY (A11 IN 43 PATIENTS: HYPERSECRETION: A CAUSE OF VIRILISATION OR PREMATURE CLASSIFICATION BASED ON CLINICAL AND ANDROGEN PUBARCHE IN PREPUBERTAL GIRLS RECEPTORS CAR) PHENOTYPES. Androgen binding was studied in genital skin fibroblasts (GSF) In two unrelated girls with signs of excessive androgen pro- established from XY patients with testes displaying signs of duction ,the usual causes (premature adrenarche, mild congenital complete androgen insensitivity syndrome (CAIS, n = 14) and partial adrenal hyperplasia, adrenal or ovarian tumor) were excluded. Pa- AIS (n = 29). Total whole-cell AR concentrati.on (Bmax) in GSF tient 1 presented at age 3.6 (bone age (BA) 3.75) yrs with hyper- strains derived from 31 normal circumcised boys was 775 * 185 x trophy (3cm) of the clitoris and erections. Urinary total 17KS 10-% mollpg DNA (mean f SD). The AR phenotype was receptor- (0.7mgId) and individual steroids (5-pregnenetrio1,pregnanetriol- negative in 79% of CAIS patients; however, the remaining 21% in one,THS,THDOC,individual 17KS) and plasma DHEA(4.8) and 170HP(2.7 this series had su ranormal AR concentrations (mean 1840, range nmolll) Were n0rmal.Plasma estradiol (E2,142pmol/l) Was minimally 1541 - 2072 x 10-1f mollpg DNA). Further studies on these cell elevated,but testosterone (T,8.2) and androstenedione (A,10.4nmol strains showed stable androgen binding at 4PC, normal 11) were high. At laparotomy, ovarian cysts without evidence of a dissociation rate for the AR complex, appropriate GSF cytosol tumor were found and removed. After surgery, T(0.7) and A(1.6nmol sedimentation on sucrose density gradients in the presence of /l )returned to normal and remained so during 5yrs of observation. molybdate and 60% binding of the androgen Ligand located in the The clitoris did not change, but erections occurred no longer. nuclei. Only 7% of GSF strains from patients with PAIS were Patient 2 presented at 7.8 (BA 9.1) yrs with pubic (stage 2) and AR-negative; mean * SD concentration of AR in the remainder was axillary hair. Urinary 17KS(1.9 mgld) and individual steroids, as 837 f 315 x 10-18 mollpg DNA. No PAIS cell strain contained well as plasma DHEA(7.7),170HP(3.3nmol/l),and E2(139pmol/l) were a supranormal AR concentration. More than 90% of AR-positive normal, but T (7.7) and A (8.1 nmolll) were elevated. Echography cell strains (including those with supranormal AR Levels) showed polycystic ovaries. Without treatment, T (1.9) and A (2.1 responded by further augmenting total cellular AR concentration nmol1l)dropped to normal during 3 subsequent yrs, and appropriate following prolonged androgen preincubation of GSF. This AR puberty started later. Transiently increased ovarian T and A of phenotype is not the result of a mutation affecting the gene unknown cause has to be included in the differential diagnosis of coding for the AR protein. excessive androgen production in prepubertal girls. Supported by Swiss National Science Foundation. (Grant 3874083) 1199