Oestrone (E1), oestradiol (E2), testosterone (T), androstenedione (A) and cortisol (F) as well as LH and the percentage of binding of E1, E2, T and F in plasma were measured and compared in normal young and old male subjects and in male patients with fatty liver, chronic hepatitis and cirrhosis of the liver. The alterations seen were most marked in the cirrhotic patients, but were partially also found in patients with fatty liver and in normal old subjects: a definite increase in E1, a smaller increase in E2, a decrease in T and a rise in LH. F remained unchanged. The ratios of E2/T and E1/T were higher in cirrhotic patients than in healthy young subjects. As the percentage of bound T in plasma rose, the oestrogen/androgen imbalance was greater in patients with liver disease and in old subjects than the ratio of total hormone plasma concentration indicates. The biological relevance of the extremely high E1 plasma concentrations in patients with cirrhosis of the liver is not known. It is suggested that the combination of elevated E1 and E2 and reduced T, which is strongly bound by increased sexual hormone binding globulin (SHBG) may be responsible for gynaecomastia and hypogonadism in chronic liver diseases. As similar alterations of steroid plasma concentrations and their binding to plasma proteins are found both in patients with liver disease and in old men, these changes may be caused by the same mechanism: namely an altered liver function.

Of 44 male patients with idiopathic hemochromatosis who were diagnosed at an early stage without morphological or biochemical evidence of liver disease, 25% suffered from impotence and 34% manifested glucose intolerance. Impotence was correlated with a 50% reduction in plasma testosterone, resulting from a 63% decrease in testosterone production. Testicular atrophy was caused by insufficient secretion of gonadotropins due to the selective accumulation of iron in gonadotropic cells of the pituitary gland. However, peripheral sexual hormone metabolism, in particular the conversion of androgens to estrogens, remained unaltered. It was therefore possible to employ substitution therapy successfully with testosterone in these men, and hyperestrogenism was not observed as a side effect. The pathogenetic factors in the development of diabetes mellitus in patients with idiopathic hemochromatosis include impaired insulin secretion caused by the selective deposition of iron in B-cells of the pancreas and insulin resistance due to iron accumulation in the liver. In particular, the insulin resistance is markedly improved after depletion of body iron stores by phlebotomy treatment, resulting in lower insulin requirements in patients with insulin-dependent diabetes as well as improvement of carbohydrate metabolisms in about half of the patients with non-insulin-dependent diabetes. We have concluded that hypogonadism and carbohydrate intolerance are caused by the specific distribution pattern of excess iron in the organism, accompanied by functional impairment of affected parenchymal cells.

The effect of a new analogue of the gonadotrophin-releasing hormone LH-RH, D-Ser(TBU)⁶-EA¹⁰-LH-RH, on the secretion of LH, FSH, as well as testosterone, oestrone, oestradiol, HGH, prolactin, TSH, and cortisol was studied in normal men. The same subjects were injected intravenously in 4-day intervals with 1.0, 2.5, 5.0, and 10.0 µg of this substance. A significant LH but no FSH release was seen after doses of 1.0 and 2.5 µg LH-RH analogue, while after 5.0 and 10.0 µg dose-dependent increases of LH and imposed elevations of FSH were observed. Peak levels of LH were reached after 30 min, those of FSH after intravenous injection after 120 min. LH and FSH remained elevated for 8–10 h. LH peak levels after 5 µg of LH-RH analogue were comparable to those seen after injection of 100 µg of the decapeptide LH-RH. Following the release of LH and FSH after doses of 5.0 and 10.0 µg LH-RH analogue, there was a late stimulating effect in testosterone and oestradiol secretion. HGH, TSH, prolactin, and cortisol were not influenced by the LH-RH analogue.

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The androgen receptor in fibroblasts cultured from a biopsy of scrotal skin from 1 subject with Reifenstein syndrome has been found to be normal in amount and to bind dihydrotestosterone with normal affinity but to be qualitatively abnormal as evident by thermolability and instability upon ultracentrifugation. The family study of this subject and endocrine studies document androgen resistance in the index patient and his affected uncle. These findings provide evidence for X-linkage of this disorder, and suggest that the mutations that give rise to this phenotype are probably allelic to the mutations of the androgen receptor that cause testicular feminization.

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Zusammenfassung:In Inkubationsversuchen mit 2. Im Metabolit-Muster gibt sich die Feminisierung Leberschnitten wurde der Stoffwechsel von Testo-der behandelten Tiere in einer gegenüber den steron studiert, und zwar bei sexuell normal ent-Kontrolltieren signifikant kleineren Bildungsrate wickelten, 130 Tage alten männlichen Ratten und (Faktor 0,15) von Androstendion und einer signibei gleichaltrigen und gleichgeschlechtlichen Ratten fikant größeren Produktionsrate von 5a-konfigunach Eingriff in die sexuelle Entwicklung durch rierten Dihydro-und Tetrahydro-Verbindungen einmalige Injektion von 300 g Östradiol-benzoat mit zum Teil hoher biologischer Aktivität zu eram 4. Lebenstag.kennen: 17ß-Hydroxy-5a-androstan-3-on (Faktor Die neonatale Injektion von Östradiol-benzoat 2,4); 5a-Androstan-3a,17ß-diol (Faktor 15) und führt zu persistierenden Alterationen im Stoff-Androsteron (Faktor 27). Wechsel, die als Feminisierung zum Ausdruck In den biologisch inaktiven Metaboliten Epiandrokommen. Folgende sexualtypische Parameter zei-steron und 5oc-Androstan-3ß,17ß-diol sind die gen bei den entwicklungsgestörten Tieren ein-Metabolit-Muster beider Tierkollektive identisch, deutig femininen Charakter:Der durch den neonatalen Eingriff herbeigeführten 1. Gegenüber den normalen Kontrolltieren hat die Feminisierung fehlt es somit an letzter Vollständig-Leber der behandelten Tiere eine höhere Steroid-keit. Retention (Faktor 1,4), eine größere Hydrogenierungsaktivität (Faktor 1,6) und eine kleinere Hydroxylierungsaktivität (Faktor 0,8). Alterat ions in testosterone metabolism following experimental interference with the sexual development of the activity pattern of rat liver enzymes involved in steroid hormone metabolismSummary: Testosterone metabolism was studied in old male rats and from male rats of the same age 1 iver si ices from sexually normally developed 130day after interference with the sexual development by * Postanschrift: Prof. Dr. H. Schriefers, A 4 -5oc-Hydrogenase, Cortison-a-Reduktase, 4,5-a-Dihydrocortison:NADP-A 4 -Oxidoreduktase (EC 1.3.1.4) Steroid-Hydroxylasen, Steroid, NADPH:Sauerstoff-Oxidoreduktase (l Iß-bzw. 17 -bzw. 21-hydroxylierend) (EC 1.14.1.6 bzw. 7 bzw. 8). Abkürzungen: Androstandion = 5a-Androstan-3,17-dion; Androstendion = 4-Androsten-3,17-dion; Androsteron = 3a-Hydroxy-5a-androstan-17-on; Cortisol = llß,17a,21-Trihydroxy-4-pregnen-3,20-dion; Epiandrosteron = 3ß-Hydroxy-5oc-androstan-17-on; Östradiol-benzoat = l,3,5(10)-Östratrien-3,17ß-diol-3-benzoat; Testosteron = I7ß-Hydroxy-4-androsten-3-on; KHR-Lösung = Krebs-Henseleit-Ringer-Lösung.Brought to you by | Purdue University Libraries Authenticated Download Date | 6/3/15 8:47 PM

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