- Email: [email protected]
8C. Adrenal cortex and pregnancy 295. Stimulation of the human fetal adrenal by ACTH and its role in parturition
366
Abstracts
elevated during the six following hours. In five patients Lasix was administered by i.v. infusion (40 mg in 3 h). The general pattern was similar but urinary levels return to normal at the third hour, while the infusion was still continuing. Such largeincrease of urtnary estrogen excretion wtthout any major modification of serum level suggests a mechanism adjusting the concentration of circulating estrogens either by rapid mobilisation of estrogen storage or by an increase of feto-placental biosynthesis. This might have some implications in the use of estrogen assay for the monitoring of high-rish pregnanctes.
8C. Adrenal cortex and pregnancy 295. Stimulation of the human fetal adrenal by ACTH and its role in parturition *SWAAB, D. F. and JFHONNEBIER,W. J., *Netherlands Central Institute for Brain Research, Amsterdam. the Netherlands, and tDepartment of Obstetrics and Gynaecology. University of Amsterdam. the Netherlands With the ultimate aim of ending useless anencephalic pregnancies. we studied whether administration of ACTH or HCG would stimulate the fetal adrenals and initiate parturition. The fact of anencephaly and the purpose of our investigations were fully explained to the pregnant women, The hormones were injected directly into the fetus in utero. The effect of this stimulation was followed by measuring maternal oestrogen secretion and the adrenals were examined both histologically and histochemically. No effect of HCG on the fetal adrenals could be demonstrated. ACTH did stimulate fetal adrenal growth and function. although it appeared that an enormous amount of ACTH was required to obtain a relatively moderate increase in both adrenal growth and function. This led to the suggestion that other adrenotropic factors must be operative in the normal intra-uterine condition. In order to determine the intluence of the human fetal hypothalamohypophysial-adrenal system upon gestation length. 147 pregnancies with anencephaly were analyzed and compared with a control group. The mean gestation length was significantly shorter in the anencephalic group than in the control group. Spontaneously born anencephalics from pregnancies with no hydramnios had a mean gestation length which wasnot significantly different from that of the control group. Our observations do not support the suggestion that the anencephalic fetus might be the human analogue to the hypophysectomized lamb. nor that the pituitary-adrenal axis. of importance in the initiation of labour in sheep, plays the same role in humans. 296. Ontogeny of secretion and control of ovine foctal adrenal cortex WINTOL’R. MARELYN E.. BROWN. E. H.. HARDY. A. K., MCDOLIGALL, J. G., ODDIE, C. J. and WHIPP. G. T.. Howard Florey Institute and Department of Physiology. University of Melbourne, Victoria. Australia The major aims were the studies of the ontogeny of steroid secretions by the ovine foetal adrenal cortex and regulatory mechanisms. Adrenal glands from foetuses aged 40 days to term (147 days) were incubated and aldosterone (aldo), corticosterone (B) and cortisol (F) production rates measured by a double isotope dilution derivative assay.
Glands of 8 foetuses aged 40 days produced measurable quantities of all 3 steroids, Aldo production rate (APR) was highest in foetuses 60-90 days gestation. 243 (SD. 0.55) ng/mg adr./2 h incubatton and was not increased hy raising the K’ concentration from 3 -5 -8 mEq I. Rcsponstveness of APR to K’ was establtshed hy the 130th day. ACTH produced a highly significant increment In all 3 steroid productions in 60-90 day period (APR from I .76 to 6.4. FPR from I.23 --r27,8 ng,mg’2 h). The ch’ect of AC‘TH on F and B production declined to reach a nadir about the 120th day and then returned to be markedly stimulatory in the week before parturition. Foetal peripheral blood values for aldo and DOC vverc 4.5 (S.D. 1.2) and 0.1 (5 7) ng/lOOml respectively, and for F 0.55 (0-3X). B O.I?( 0.10) and S 0.08 (0.07) ~~g,‘lOOml in 25 samples from 60- I.15 day foetuses. The conclusion is that the ovine foetal adrenal is active quite early and responds marhedly to ACTH stimulation. 297. Pregnancy-induced Cushing’s syndrome DE MEY,~s. P..*+ MARG~~II.IES. M..? LAMROTII., R.: and VA& CAL-wtha~~tit., H.:I- University of Liege (Belgium-~ DepartmentsofMedicinctandObstetrica$ *Fellow of the Belgian F.N.R.S. Gushing’s syndrome occurring during pregnancy is a rare clinical entity. In one such 17 year-old patient. we have studied the adrenal dysfunction and its effrcts on the pregnancy and on the fetal steroid secretton. Endocrine studies revealed elevated urinary I7-hydroxycorticosteroids and plasma cortisol with lack of diurnal variation. and no response to ACTH, metopirone. hypoglycemia or dcxamethasone suppression. The cortisol binding globulin in plasma was abnormally low; plasma testosterone and sex binding globulin high. Other pituitary functions were normal as judged by stimulation with LHRH, TRH and hypoglycemia. Chemical diabetes with marked hyperinsulinism developed. Placental function was evaluated at ditfercnt stages. Oestriol levels appeared normal, but failure to transform dehydroepiandrosteronc was demonstrated at the 7th month. At that point. placental lactogen. abnormally high, had reached levels normally found at full term and a 3.06 pounds girl was delivered spontaneously at 7 months. Two months post-partum, the syndrome was more advanced and a bilateral adrenalectomy revealed micronodular bilateral hyperplasia. confirmed by light and electron microscopy. Itz ~i/ru. the adrenal glands continued to demonstrate autonomous secretion and insensitivity to ACTH. The newborn showed a normal cortisol response tc) hypoglycemia, demonstrating a lack of etTect of maternal hypercortisolism on the development of the fetal pituitaryadrenal axis. The possible presence of ACTH-like materials in the placental tissue is being investtgated. 298. The effects of ACTH in adrenalectomized pregnant women VILLANUEVA, G. A., RODRIGUFZ. A. J.. ALTAMIK~\NO. M. M. and SCHIAFFINI. C.. Hormone Laboratory H.G.O. No. 3. I.M.S.S. Mextco, D.F. The purpose of this study is to tind out what effect ACTH may have on pregnant women with earlier Cushing’s syndrome and bilateral adrenalectomy. Assays were made of l7-KS. 17-OHCS, I7-KGS, pregnanediol and E,. Replacement therapy was 50 mg of cortisone orally every day. The dose was reduced every 4 days, starting with 50mg. making a progressive reduction of 17.5 mg per period. until
Abstracts
elevated during the six following hours. In five patients Lasix was administered by i.v. infusion (40 mg in 3 h). The general pattern was similar but urinary levels return to normal at the third hour, while the infusion was still continuing. Such largeincrease of urtnary estrogen excretion wtthout any major modification of serum level suggests a mechanism adjusting the concentration of circulating estrogens either by rapid mobilisation of estrogen storage or by an increase of feto-placental biosynthesis. This might have some implications in the use of estrogen assay for the monitoring of high-rish pregnanctes.
8C. Adrenal cortex and pregnancy 295. Stimulation of the human fetal adrenal by ACTH and its role in parturition *SWAAB, D. F. and JFHONNEBIER,W. J., *Netherlands Central Institute for Brain Research, Amsterdam. the Netherlands, and tDepartment of Obstetrics and Gynaecology. University of Amsterdam. the Netherlands With the ultimate aim of ending useless anencephalic pregnancies. we studied whether administration of ACTH or HCG would stimulate the fetal adrenals and initiate parturition. The fact of anencephaly and the purpose of our investigations were fully explained to the pregnant women, The hormones were injected directly into the fetus in utero. The effect of this stimulation was followed by measuring maternal oestrogen secretion and the adrenals were examined both histologically and histochemically. No effect of HCG on the fetal adrenals could be demonstrated. ACTH did stimulate fetal adrenal growth and function. although it appeared that an enormous amount of ACTH was required to obtain a relatively moderate increase in both adrenal growth and function. This led to the suggestion that other adrenotropic factors must be operative in the normal intra-uterine condition. In order to determine the intluence of the human fetal hypothalamohypophysial-adrenal system upon gestation length. 147 pregnancies with anencephaly were analyzed and compared with a control group. The mean gestation length was significantly shorter in the anencephalic group than in the control group. Spontaneously born anencephalics from pregnancies with no hydramnios had a mean gestation length which wasnot significantly different from that of the control group. Our observations do not support the suggestion that the anencephalic fetus might be the human analogue to the hypophysectomized lamb. nor that the pituitary-adrenal axis. of importance in the initiation of labour in sheep, plays the same role in humans. 296. Ontogeny of secretion and control of ovine foctal adrenal cortex WINTOL’R. MARELYN E.. BROWN. E. H.. HARDY. A. K., MCDOLIGALL, J. G., ODDIE, C. J. and WHIPP. G. T.. Howard Florey Institute and Department of Physiology. University of Melbourne, Victoria. Australia The major aims were the studies of the ontogeny of steroid secretions by the ovine foetal adrenal cortex and regulatory mechanisms. Adrenal glands from foetuses aged 40 days to term (147 days) were incubated and aldosterone (aldo), corticosterone (B) and cortisol (F) production rates measured by a double isotope dilution derivative assay.
Glands of 8 foetuses aged 40 days produced measurable quantities of all 3 steroids, Aldo production rate (APR) was highest in foetuses 60-90 days gestation. 243 (SD. 0.55) ng/mg adr./2 h incubatton and was not increased hy raising the K’ concentration from 3 -5 -8 mEq I. Rcsponstveness of APR to K’ was establtshed hy the 130th day. ACTH produced a highly significant increment In all 3 steroid productions in 60-90 day period (APR from I .76 to 6.4. FPR from I.23 --r27,8 ng,mg’2 h). The ch’ect of AC‘TH on F and B production declined to reach a nadir about the 120th day and then returned to be markedly stimulatory in the week before parturition. Foetal peripheral blood values for aldo and DOC vverc 4.5 (S.D. 1.2) and 0.1 (5 7) ng/lOOml respectively, and for F 0.55 (0-3X). B O.I?( 0.10) and S 0.08 (0.07) ~~g,‘lOOml in 25 samples from 60- I.15 day foetuses. The conclusion is that the ovine foetal adrenal is active quite early and responds marhedly to ACTH stimulation. 297. Pregnancy-induced Cushing’s syndrome DE MEY,~s. P..*+ MARG~~II.IES. M..? LAMROTII., R.: and VA& CAL-wtha~~tit., H.:I- University of Liege (Belgium-~ DepartmentsofMedicinctandObstetrica$ *Fellow of the Belgian F.N.R.S. Gushing’s syndrome occurring during pregnancy is a rare clinical entity. In one such 17 year-old patient. we have studied the adrenal dysfunction and its effrcts on the pregnancy and on the fetal steroid secretton. Endocrine studies revealed elevated urinary I7-hydroxycorticosteroids and plasma cortisol with lack of diurnal variation. and no response to ACTH, metopirone. hypoglycemia or dcxamethasone suppression. The cortisol binding globulin in plasma was abnormally low; plasma testosterone and sex binding globulin high. Other pituitary functions were normal as judged by stimulation with LHRH, TRH and hypoglycemia. Chemical diabetes with marked hyperinsulinism developed. Placental function was evaluated at ditfercnt stages. Oestriol levels appeared normal, but failure to transform dehydroepiandrosteronc was demonstrated at the 7th month. At that point. placental lactogen. abnormally high, had reached levels normally found at full term and a 3.06 pounds girl was delivered spontaneously at 7 months. Two months post-partum, the syndrome was more advanced and a bilateral adrenalectomy revealed micronodular bilateral hyperplasia. confirmed by light and electron microscopy. Itz ~i/ru. the adrenal glands continued to demonstrate autonomous secretion and insensitivity to ACTH. The newborn showed a normal cortisol response tc) hypoglycemia, demonstrating a lack of etTect of maternal hypercortisolism on the development of the fetal pituitaryadrenal axis. The possible presence of ACTH-like materials in the placental tissue is being investtgated. 298. The effects of ACTH in adrenalectomized pregnant women VILLANUEVA, G. A., RODRIGUFZ. A. J.. ALTAMIK~\NO. M. M. and SCHIAFFINI. C.. Hormone Laboratory H.G.O. No. 3. I.M.S.S. Mextco, D.F. The purpose of this study is to tind out what effect ACTH may have on pregnant women with earlier Cushing’s syndrome and bilateral adrenalectomy. Assays were made of l7-KS. 17-OHCS, I7-KGS, pregnanediol and E,. Replacement therapy was 50 mg of cortisone orally every day. The dose was reduced every 4 days, starting with 50mg. making a progressive reduction of 17.5 mg per period. until