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Biomedical subjects

L Verdonck

Publications and source records attributed to L Verdonck.

At least 19 recordsLinked to original sources

A novel CBFA2 single-nucleotide mutation in familial platelet disorder with propensity to develop myeloid malignancies.

Hereditary mutations associated with hematologic malignancies are rare. Heterozygous mutations affecting the hematopoietic transcription factor CBFA2 (also AML1/RUNX1) were recently reported to be associated with familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML, MIM 601399). A new 3-generation family with FPD/AML with a novel CBFA2 mutation is described. In this family, AML was diagnosed in a second-generation male. After allogeneic stem cell transplantation from his human leukocyte antigen-identical sister, a donor-derived, genetically identical leukemia developed in the recipient and the donor. Sequencing analysis identified a G-to-T transition within the CBFA2 gene, which involves codon 198, encoding a conserved aspartic acid within the DNA- binding Runt domain. Three of 5 siblings affected with the FPD/AML trait harbored the mutation in a heterozygous form. This experience underscores the necessity of performing mutation analysis of the CBFA2 gene before sibling allogeneic transplantation in families with FPD/AML.

Acute Disease↗

Characterization of Vibrio viscosus and Vibrio wodanis isolated at different geographical locations: a proposal for reclassification of Vibrio viscosus as Moritella viscosa comb. nov.

Vibrio viscosus and Vibrio wodanis are recently described species of psychrotropic bacteria that have been found associated with a disease called 'winter ulcer', affecting salmonid fish reared in saline water in Norway, Iceland and recently in Scotland. V. viscosus and V. wodanis strains initially isolated from fish in Iceland and Norway were subjected to characterization using biochemical tests, SDS-PAGE of whole-cell proteins and a novel DNA fingerprinting method, amplified fragment length polymorphism (AFLP). The V. viscosus strains isolated from diseased fish grouped into homogeneous subgroups according to geographical origin and challenge experiments revealed that representatives of these groups are virulent. The results revealed that the V. wodanis strains are heterogeneous genotypically and phenotypically. Sequencing of almost complete 16S rRNA genes of V. viscosus and V. wodanis revealed that V. viscosus showed a 99.1% sequence similarity to Moritella marina and V. wodanis showed a 98.8% sequence similarity to Vibrio logei CIP 103204. A reclassification of Vibrio viscosus as Moritella viscosa comb. nov. is proposed.

Animals↗

Vibrios associated with Litopenaeus vannamei larvae, postlarvae, broodstock, and hatchery probionts.

Several bacteriological surveys were performed from 1994 to 1996 at different Litopenaeus vannamei hatcheries (in Ecuador) and shrimp farms (in Mexico). Samples were taken from routine productions of healthy and diseased L. vannamei larvae, postlarvae, and their culture environment and from healthy and diseased juveniles and broodstock. In Ecuador, the dominant bacterial flora associated with shrimp larvae showing symptoms of zoea 2 syndrome, mysis mold syndrome, and bolitas syndrome has been determined. Strains were characterized by Biolog metabolic fingerprinting and identified by comparison to a database of 850 Vibrio type and reference strains. A selection of strains was further genotypically fine typed by AFLP. Vibrio alginolyticus is predominantly present in all larval stages and is associated with healthy nauplius and zoea stages. AFLP genetic fingerprinting shows high genetic heterogeneity among V. alginolyticus strains, and the results suggest that putative probiotic and pathogenic strains each have specific genotypes. V. alginolyticus was found to be associated with larvae with the zoea 2 syndrome and the mysis mold syndrome, while different Vibrio species (V. alginolyticus and V. harveyi) are associated with the bolitas syndrome. V. harveyi is associated with diseased postlarvae, juveniles, and broodstock. The identities of the strains identified as V. harveyi by the Biolog system could not be unambiguously confirmed by AFLP genomic fingerprinting. Vibrio strain STD3-988 and one unidentified strain (STD3-959) are suspected pathogens of only juvenile and adult stages. V. parahaemolyticus, Photobacterium damselae, and V. mimicus are associated with juvenile and adult stages.

Animals↗

A critical evaluation of simple methods for the estimation of free testosterone in serum.

The free and nonspecifically bound plasma hormone levels generally reflect the clinical situation more accurately than total plasma hormone levels. Hence, it is important to have reliable indexes of these fractions. The apparent free testosterone (T) concentration obtained by equilibrium dialysis (AFTC) as well as the fraction of serum T not precipitated by 50% ammonium sulfate concentration (non-SHBG-T; SHBG, sex hormone-binding globulin), often referred to as bioavailable T, appear to represent reliable indexes of biologically readily available T, but are not well suited for clinical routine, being too time consuming. Several other parameters have been used without complete validation, however: direct immunoassay of free T with a labeled T analog (aFT), calculation of free T (FT) from total T and immunoassayed SHBG concentrations (iSHBG), and the free androgen index (FAI = the ratio 100T/iSHBG). In the view of substantial discrepancies in the literature concerning the free or bioavailable T levels, we compared AFTC, FT, aFT, FAI, and non-SHBG-T levels in a large number of sera with SHBG capacities varying from low, as in hirsute women, to extremely high as in hyperthyroidism. All these indexes of bioavailable T correlated significantly with the AFTC concentration; AFTC and FT values were almost identical under all conditions studied, except during pregnancy. Values for aFT, however, were only a fraction of either AFTC or FT, the fraction varying as a function of SHBG levels. Also, the FAI/AFTC ratio varied as a function of the SHBG levels, and hence, neither aFT nor FAI is a reliable index of bioavailable T. The FT value, obtained by calculation from T and SHBG as determined by immunoassay, appears to be a rapid, simple, and reliable index ofbioavailable T, comparable to AFTC and suitable for clinical routine, except in pregnancy. During pregnancy, estradiol occupies a substantial part of SHBG-binding sites, so that SHBG as determined by immunoassay overestimates the actual binding capacity, which in pregnancy sera results in calculated FT values that are lower than AFTC. The nonspecifically bound T, calculated from FT, correlated highly significantly with and was almost identical to the values of non-SHBG-T obtained by ammonium sulfate precipitation, testifying to the clinical value of FT calculated from iSHBG.

Adult↗

Phylogenetic position of phytopathogens within the Enterobacteriaceae.

The almost complete 16S rDNA sequences of twenty nine plant-associated strains, representing species of the genera Erwinia, Pantoea and Enterobacter were determined and compared with those of other members of the Enterobacteriaceae. The species of the genus Erwinia may be divided into three phylogenetic groups. Cluster I represents the true erwinias and comprises E. amylovora, E. mallotivora, E. persicinus, E. psidii, E. rhapontici and E. tracheiphila. We propose to unite the species of cluster II, E. carotovora subsp. atroseptica, E. carotovora subsp. betavasculorum, E. carotovora subsp. carotovora, E. carotovora subsp. odorifera, E. carotovora subsp. wasabiae, E. cacticida, E. chrysanthemi and E. cypripedii in the genus Pectobacterium respectively as P. carotovorum subsp. atrosepticum comb. nov., P. carotovorum subsp. betavasculorum comb. nov., P. carotovorum subsp. carotovorum comb. nov., P. carotovorum subsp. odoriferum comb. nov., P. carotovorum subsp. wasabiae comb. nov., P. cacticidum comb. nov., P. chrysanthemi and P. cypripedii. The species E. alni, E. nigrifluens, E. paradisiaca, E. quercina, E. rubrifaciens and E. salicis, comprising cluster III, are being classified into a new genus Brenneria gen. nov. respectively as B. alni comb. nov., B. nigrifluens comb. nov., B. paradisiaca comb. nov., B. quercina comb. nov., B. rubrifaciens comb. nov. and B. salicis comb. nov. The species of the genus Pantoea, included in this study, form a monophyletic unit (cluster IV), closely related with Erwinia, whereas the three phytopathogenic species of the genus Enterobacter are scattered among the genera Citrobacter and Klebsiella.

Bacterial Typing Techniques↗

Typing of the fish pathogen Listonella (Vibrio) anguillara by pyrolysis mass spectrometry.

Twenty-eight representatives of Listonella (Vibrio) anguillara serovars O1, O2 and O3 were compared by Curie-point pyrolysis mass spectrometry (PyMS). The representatives of serovars O1 and O3 formed discrete, homogeneous groups in ordination plots of the PyMS data. Strains from serovar O2 were recovered in two groups, one of which encompassed six strains including the type strain of the species and the reference strain for serovar O2, and the other included two strains which showed cross-reactions between serovars O2 and O5. The almost complete agreement found between the PyMS and the serological data suggests that pyrolysis mass spectrometry will prove to be an effective method for interstrain comparison within the species Listonella anguillara.

Animals↗

Intraspecific Differentiation of Vibrio vulnificus Biotypes by Amplified Fragment Length Polymorphism and Ribotyping.

The intraspecific genomic relatedness of 80 Vibrio vulnificus isolates, 44 of biotype 1 and 36 of biotype 2, from different geographic origins and sources was evaluated by ribotyping and AFLP (amplified fragment length polymorphism) fingerprinting. Ribopatterns of DNAs digested with KpnI and hybridized with an oligonucleotide complementary to a highly conserved sequence in the 23S rRNA gene revealed up to 19 ribotypes in the species, which were different for the two biotypes. Sixteen different ribotypes were found within biotype 1 strains from clinical and environmental sources, and only three, recovered mainly from diseased eels, were found within biotype 2. Within this biotype, 96% of the strains showed the same ribopattern. The closest similarity was shown by the strains coming from the same eel farm, irrespectively of biotype. AFLP fingerprints obtained by selective PCR amplification of HindIII-TaqI double-restricted DNA fragments exhibited a strain-specific pattern which allowed the finest differentiation of subgroups within the eel-pathogenic isolates sharing the same ribopattern. Both techniques revealed good genetic markers for intraspecific differentiation of V. vulnificus. Ribotyping clearly separated the eel-pathogenic strains from the clinical and environmental isolates, whereas AFLP enabled the monitoring of individual strains and therefore constitutes one of the most discriminative tools for epidemiological and ecological studies.

Journal Article↗

Graft-versus-leukemia effect of donor lymphocyte transfusions in marrow grafted patients.

The immune reactivity of allogeneic lymphocytes plays a major role in the control of leukemia after bone marrow transplantation. In patients with recurrent leukemia after marrow transplantation, chimerism and tolerance provide ideal conditions for adoptive immunotherapy with donor lymphocytes. We studied the effect of donor lymphocyte transfusions on acute and chronic leukemia in relapse after bone marrow transplantation. One hundred thirty-five patients with chronic myeloid leukemia (CML) (N = 84), acute myeloid leukemia (AML) (N = 23), acute lymphoblastic leukemia (ALL) (N = 22), myelodysplastic syndrome (MDS) (N = 5), and polycythemia vera with osteomyelofibrosis (PCV) (N = 1) were treated with transfusions of donor lymphocytes. Patients were monitored for response of leukemia, including in CML, the use of the polymerase chain reaction for bcr/abl mRNA transcripts and for the occurrence of graft-versus-host disease (GVHD) and myelosuppression. Complete remissions were induced by donor lymphocyte transfusions in 54 patients with CML (73%) and in the patient with PCV; complete remissions were also induced in five patients (29%) with AML and a patient with MDS. In contrast, ALL did not respond to adoptive immunotherapy with donor lymphocyte transfusions. Remissions were durable in patients treated for CML in chronic phase (probability of remission: 87% at 3 years). Lymphocyte transfusions were also given to 18 patients with ALL, AML, MDS, and transformed phase CML who were in remission after chemotherapy. These remissions were not durable. Fifty-two patients (41%) developed GVHD of grade 2 or more, and 41 patients (34%) showed signs of myelosuppression. Seventeen patients died without leukemia, 14 patients with GVHD and/or myelosuppression. Donor lymphocyte transfusions exert strong effects against myeloid forms of leukemia and induce durable remissions in CML.

Adolescent↗

Androgens in seminal plasma: markers of the surface epithelium of the male reproductive tract.

Androgens in seminal plasma have been investigated in relation to other markers of the male reproductive system. Testosterone and dihydrotestosterone (DHT) were measured by radioimmunoassay after paper chromatography in 104 semen samples. Concentrations of testosterone and DHT were significantly lower in samples from patients with abnormal sperm characteristics than in men with normozoospermia. Both testosterone and DHT were correlated significantly with sperm concentration (r = 0.40, p < 0.001; r = 0.41, p < 0.001, respectively), motile sperm concentration (r = 0.35, p < 0.01; r = 0.35, p < 0.01) and ATP concentration (r = 0.59, p < 0.001; r = 0.45, p < 0.001). In addition, the total amounts of testosterone and DHT were correlated with total activity of alpha-glucosidase (r = 0.49, p < 0.001; r = 0.58, p < 0.01), and gamma-glutamyltransferase (r = 0.49, p < 0.001; r = 0.48, p < 0.001) in seminal plasma. Transferrin (Tf) concentration in seminal plasma was significantly lower in samples without spermatozoa, and total Tf content was lower in oligozoospermic samples (p < 0.05). Testosterone and DHT were correlated positively with Tf levels in seminal plasma (r = 0.48, p < 0.0001; r = 0.78, p < 0.0001 respectively). Testosterone, DHT and Tf in seminal plasma were higher in the first than in the second fraction of split ejaculates, and DHT, but not testosterone, increased significantly in each of six patients treated with tamoxifen. Testosterone, DHT, and Tf in seminal plasma were not correlated with serum concentrations of LH, FSH, testosterone or prolactin, but the DHT : T ratio in seminal plasma was correlated with serum LH (r = 0.36, p < 0.05). It is concluded that the concentration of androgens in seminal plasma is related predominantly to the activity of the seminiferous epithelium and, to a lesser extent, to the function of the accessory sex glands.

Adenosine Triphosphate↗

A randomized study in stage IIIB and IV Hodgkin's disease comparing eight courses of MOPP versus an alteration of MOPP with ABVD: a European Organization for Research and Treatment of Cancer Lymphoma Cooperative Group and Groupe Pierre-et-Marie-Curie controlled clinical trial.

PURPOSE: We report a prospective randomized study comparing the relative efficacy of alternating chemotherapy mechlorethamine, vincristine, procarbazine, and prednisone/doxorubicin, bleomycin, vinblastine, and dacarbazine (MOPP/ABVD) with the standard MOPP chemotherapy in patients with stage IIIB and IV Hodgkin's disease (HD). The purpose is to study the influence of time of remission on clinical outcome. PATIENTS AND METHODS: After two courses of MOPP, patients were randomized to receive six further courses of MOPP, or two courses of ABVD followed by two courses of MOPP and two courses of ABVD. Radiotherapy was given to areas presenting with masses > or = 5 cm and to residual masses after course no. 4. Evaluation of response (complete remission [CR]) took place after two courses (CR2), after four courses (CR4), at the end of chemotherapy (CR8), and after additional radiotherapy (CR(CT + RT)). Logistic regression analysis was used to study prognostic factors for response at the end of chemotherapy. Cox analysis was used to study prognostic factors for survival. Two hundred seven patients were registered, 192 (93%) of whom were randomized. RESULTS: The CR rate at the end of chemotherapy (CR8) was similar in both arms (57% v 59%). However, there were more progressions in the MOPP arm compared with the MOPP/ABVD arm (23% v 8%, P = .014). A significantly higher failure-free survival (FFS) rate was found in the MOPP/ABVD arm (60% v 43% at 6 years, P = .025). There was no difference in the relapse-free survival (RFS) or survival rate. Of patients not in CR4, only 28% still reached a CR8. RFS at 6 years of patients with CR4 (69%) was not different from that of patients with CR8 (68%); patients with a CR(CT + RT)) had a lower RFS rate (48%). CR4 (P < .001) predicted strongly for final remission at the end of chemotherapy. Cox analysis showed that age more than 50 years, six or more involved lymph node areas, no CR by the fourth cycle, chemotherapy with MOPP alone, and no radiotherapy were unfavorable factors for survival. CONCLUSION: MOPP/ABVD chemotherapy significantly improved response and FFS rates, but had no influence on RFS and survival rates. Early CR (CR4) is an important factor for final remission and might be used to select a group of patients with a good prognosis.

Adolescent↗

Bone marrow transplantation for acute myeloblastic leukaemia: an EBMT Leukaemia Working Party prospective analysis from HLA-typing.

The optimal post-remission therapy for patients with acute myeloblastic leukaemia remains controversial. Allogeneic bone marrow transplantation, autologous bone marrow transplantation, and consolidation chemotherapy are the major options. In order to evaluate their respective value the European Group for Bone Marrow Transplantation conducted a prospective registration study. Patients with newly diagnosed acute myeloblastic leukaemia were registered at the time of HLA-typing and intention to treat in case of presence or absence of an HLA-identical donor was recorded. 27/79 (34%) patients HLA-typed at diagnosis had an identical donor identified. The estimated survivals at 3 years from HLA-typing were 44% and 21% among patients with or without HLA-identical donor, respectively (P = 0.02). 22/26 (85%) patients for whom allogeneic bone marrow transplantation was intended were transplanted but only 15/47 (32%) patients for whom autologous bone marrow transplantation was intended were indeed transplanted (P < 0.001). The survival was 50%, 29% and 17% (P = 0.004) for patients treated with allogeneic bone marrow transplantation, autologous bone marrow transplantation, or chemotherapy, respectively. 40/68 patients HLA-typed in first complete remission had an HLA-identical donor. The estimated 3-year survival among patients typed in first remission with and without HLA-identical donors was 42% and 35% (n.s.), respectively. This technique of early patient registration illustrates the problems of patient selection during the course of the disease and might be used as a complement to randomized trials when comparing bone marrow transplantation and other treatment options.

Adolescent↗

Comparison of plasma androgen glucuronide levels after percutaneous or peroral androgen treatment in men: evidence for important splanchnic contribution to plasma 17 beta-hydroxyandrogen glucuronides.

To investigate whether glucuronides of 17 beta-hydroxyandrogens are formed mainly in peripheral tissues or in splanchnic tissues, we compared androstanediol (AD) glucuronide (ADG) and dihydrotestosterone (DHT) glucuronide (DHTG) levels as well as the ratios of glucuronides over free steroids after transcutaneous DHT gel administration to levels and ratios found after oral administration of testosterone undecanoate. Whereas DHT and AD plasma levels were much higher after transcutaneous DHT gel administration, ADG and DHTG levels as well as glucuronide/free androgen ratios were an order of a magnitude higher after oral TU. This indicates that 17 beta-hydroxyandrogen glucuronides cannot be considered specific metabolites of androgen target tissues and are formed to a large extent in the splanchnic circulation.

Administration, Cutaneous↗

Bone marrow transplantation for acute myeloid leukemia: the EBMT experience. A prospective analysis from HLA-typing. The EMBT Leukemia Working Party.

In 1990, 4,234 BMT were performed in Europe; 2,097 autologous BMT (388 AML) and 2,137 allogeneic BMT (494 AML). Although an established therapy with leukemia free survival (LFS) at five years of 41% +/- 5% (EBMT results) its value compared to alternative therapies remains controversial. During the year 1985, the EBMT conducted a prospective evaluation study. In 12 centres 168 patients with AML were registered at the time of HLA-typing. Basic patient data and treatment intention were recorded. 79 patients were HLA-typed at diagnosis. 68 patients in 1st CR and 21 at other stages. Follow-up of these patients was obtained as of January 1, 1991. Three-year LFS is 44% for patients with an HLA-identical donor and 21% for those without (p = 0.02). Of the 68 patients HLA-typed in first CR, 40 had an HLA-identical donor and 28 no donor. Three-year LFS is 42% and 35%. resp. (n.s.). The difference in results between patients typed at diagnosis and first CR patients illustrates the problem of selection. We conclude that patient registration early in the disease can give insight into the process of selection. Allogeneic BMT incorporated prospectively at diagnosis into therapy offers a survival advantage for patients in this age category compared to alternative therapies.

Acute Disease↗

Precursors of plasma androstanediol- and androgen-glucuronides in women.

Although androstanediol (AD) and androstanediolglucuronide (ADG) are generally considered to be parameters of peripheral androgen action, their plasma levels do not always vary in parallel, suggesting that they may have different precursors. Few hard data being available concerning ADG precursors in women, we studied in postmenopausal women with absent or suppressed adrenal function, the blood conversion rates of testosterone (T), dihydrotestosterone (DHT), androstenedione (A) and dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) to AD and ADG respectively, as well as the conversion of AD to ADG. Moreover conversions of these precursors to testosteroneglucuronide (TG) and dihydrotestosteroneglucuronide (DHTG), respectively, were also studied. Our data show that, whereas plasma A and DHT are the major precursors of AD, plasma DHEAS and A are the major precursors of plasma ADG, accounting for 50 and 15%, respectively, of plasma ADG, A being the major precursor of plasma TG and DHTG, respectively. When the conversion rates, obtained in this study, were applied to the plasma concentration of precursors found in normal young and postmenopausal women, respectively, the calculated concentration of product steroids accounted for almost the totality of the actual plasma levels of ADG, TG and DHTG respectively. The difference in relative importance of their precursors, explains that plasma concentrations of AD and ADG do not always vary in parallel; moreover, the importance of DHEAS as precursor of ADG explains the suppression by dexamethasone and the increase after adrenocortical stimulation of plasma ADG levels.

Adult↗

Fat tissue: a steroid reservoir and site of steroid metabolism.

Sex steroid concentrations and 17 beta-hydroxy-steroid dehydrogenase and aromatase activities were determined in fat tissue removed at surgery or, in order to allow comparisons in different sites, postmortem. Except for dehydroepiandrosterone (DHEA) sulfate (DHEAS), there existed a positive tissue/plasma gradient for all steroids studied (testosterone, androstenedione, DHEA, androstenediol, estrone, and estradiol), suggesting androgen uptake and estrogen synthesis in situ. Androgen concentrations did not vary according to site of origin of fat tissue, except that the DHEAS concentration was significantly lower in abdominal sc and omental fat than in breast, pericardial, or sc pubic fat. Tissue androgen concentrations were positively correlated with their plasma concentrations, but tissue and plasma estrogen concentrations were not correlated. All tissue steroid concentrations, with the exception of estradiol in men, decreased with age. Aromatase activity [androstenedione----estrone; mean maximum velocity, 7.4 +/- 3.7 (+/- SD) fmol estrone/mg protein . h] did not vary between sexes or with site of origin of fat tissue. 17 beta-Hydroxysteroid dehydrogenase activity (estradiol----estrone, mean maximum velocity 9.8 +/- 5.4 pmol/mg protein . h) was higher in fat from women than in that from men, higher in premenopausal than in postmenopausal women, and higher in omental than in sc fat. Its activity was noncompetitively inhibited in vitro by DHEA and DHEAS in near-physiological concentrations, and the enzyme activity was inversely correlated (P less than 0.001) with the tissue DHEA and DHEAS concentrations. We conclude that fat tissue is an important steroid hormone reservoir, that it is the site of active aromatase and 17 beta-hydroxysteroid dehydrogenase, and that tissue DHEA(S) may have a modulating effect on tissue estrogen production.

17-Hydroxysteroid Dehydrogenases↗

Androgen and precursor levels in serum and testes of adult rats under basal conditions and after hCG stimulation.

In adult male Wistar rats, serum and testicular concentration of testosterone (T), estradiol (E2), dihydrotestosterone (DHT), 5 alpha-androstane 3 alpha, 17 beta-diol (Adiol), and their precursors were measured under basal conditions as well as 4 and 8 h respectively after i.m. injection of 100 I.U. of hCG. Under basal conditions T (203 +/- 30 (SE) ng/dl) was quantitatively by far the most important serum steroid, followed by progesterone (P) (76.5 +/- 12 ng/dl), 17-hydroxyprogesterone (170HP) (37.3 +/- 4.1 ng/dl), androstenedione (A) (24.6 +/- 2.5 ng/dl) and pregnenolone (P5) (22.9 +/- 4 ng/dl). Estradiol (E2) was present in a low concentration (1.06 +/- 0.26 ng/dl). In the testes, T was quantitatively the most important steroid (89 +/- 7.2 ng/g), followed by 5 alpha-androstane-3 alpha-17 beta-diol (Adiol) (26.5 +/- 2.8 ng/g) whereas 170HP (11.8 +/- 1.0 ng/g), P (11.5 +/- 1.0 ng/g) and P5 (16.6 +/- 1.8 ng/g) were present in roughly the same concentration, concentrations of A, DHT, dehydroepiandrosterone (DHEA), 17 hydroxy-pregnenolone (170HP5) and androst-5-ene-3 beta-17 beta-diol (D5diol) being much lower; E2 (0.06 +/- 0.01 ng/g) was hardly detectable. Within 4-8 h after hCG stimulation, serum androgen concentrations increased by a factor of 4-12, except for DHEA and D5diol (X2), and E2 (X 1.5). Intratesticular androgens and delta 4 steroid precursors increased by a factor of 5-10, delta 5 precursors by a factor of 2-4 and E2 by a factor of 2, the data tending to confirm that the delta 4 pathway is preferred over the delta 5 pathway. After hCG the relative increase of T precursors was the most important for P, suggesting that 17 hydroxylation might be the rate limiting step in T biosynthesis.

Androgens↗

Adrenocortical function in old age: response to acute adrenocorticotropin stimulation.

To elucidate the controversial point whether, in analogy with delta 5-steroid secretion, adrenal delta 4-steroid secretion is significantly decreased in elderly persons, we studied the response of plasma levels of both delta 5-steroids (dehydroepiandrosterone, 17-hydroxypregnenolone, and pregnenolone) and delta 4-steroids (cortisol, androstenedione, 17-hydroxyprogesterone, and progesterone) to acute ACTH stimulation in four groups of young and elderly males and females, respectively. To study the possible influence of sex hormones on adrenocortical function in elderly persons, we performed the same study in male with prostatic carcinoma treated with estrogens. The data show that in elderly persons, the response of plasma delta 4-steroids to ACTH stimulation is comparable or higher than that in young subjects, whereas the response of delta 5-steroids is significantly decreased; estrogen treatment does not change this pattern. It is concluded that in elderly persons adrenal delta 4-steroid secretory capacity is unimpaired, whereas delta 5-steroid secretion is significantly decreased. The responsible mechanism remains to be elucidated.

17-alpha-Hydroxypregnenolone↗