[Serum inhibin B as a marker of spermatogenesis].
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Biomedical subjects
Publications and source records attributed to N E Skakkeboek.
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The aim of this study was to compare results obtained by eight different short-term assays of estrogenlike actions of chemicals conducted in 10 different laboratories in five countries. Twenty chemicals were selected to represent direct-acting estrogens, compounds with estrogenic metabolites, estrogenic antagonists, and a known cytotoxic agent. Also included in the test panel were 17beta++-estradiol as a positive control and ethanol as solvent control. The test compounds were coded before distribution. Test methods included direct binding to the estrogen receptor (ER), proliferation of MCF-7 cells, transient reporter gene expression in MCF-7 cells, reporter gene expression in yeast strains stably transfected with the human ER and an estrogen-responsive reporter gene, and vitellogenin production in juvenile rainbow trout. 17beta-Estradiol, 17alpha-ethynyl estradiol, and diethylstilbestrol induced a strong estrogenic response in all test systems. Colchicine caused cytotoxicity only. Bisphenol A induced an estrogenic response in all assays. The results obtained for the remaining test compounds--tamoxifen, ICI 182.780, testosterone, bisphenol A dimethacrylate, 4-n-octylphenol, 4-n-nonylphenol, nonylphenol dodecylethoxylate, butylbenzylphthalate, dibutylphthalate, methoxychlor, o,p'-DDT, p,p'-DDE, endosulfan, chlomequat chloride, and ethanol--varied among the assays. The results demonstrate that careful standardization is necessary to obtain a reasonable degree of reproducibility. Also, similar methods vary in their sensitivity to estrogenic compounds. Thus, short-term tests are useful for screening purposes, but the methods must be further validated by additional interlaboratory and interassay comparisons to document the reliability of the methods.
Some recent studies have indicated that sperm concentration has decreased during the last 50 years. However, comparisons between laboratories have revealed that geographical differences seem to exist and that any decrease may not be global. One point of criticism concerning comparison of results from different laboratories has been that some of the discrepancies detected could reflect the lack of standardized methods used in the different laboratories. Four teams, each consisting of one physician and one technician from groups which have recently published data on semen quality, met in order to evaluate the variability between their laboratories on semen analysis. Twenty-six fresh semen samples from unselected men were analysed. The groups analysed the samples according to the normal practice in their laboratories, using their own equipment. The variation between laboratories was estimated through a random effects model. For sperm concentration and semen volume assessment a remarkable consistency between laboratories was detected, in contrast to the very considerable inter-individual variation. For sperm motility and morphology assessments interlaboratory consistency was much poorer. In conclusion, evaluation of sperm motility and morphology characteristics requires further standardization in order to achieve comparable data from different laboratories. However, semen volume and sperm concentration are characteristics which can be compared reliably between laboratories, when similar methodologies are used.
GH deficiency in children has been treated for decades with GH in order to normalize growth and final height. After cessation of linear growth GH treatment has traditionally been stopped. However, adults with GH deficiency have increased mortality due to cardiovascular disease and share several clinical signs, such as reduced muscle strength, reduced exercise capacity, reduced sweating ability and thermoregulation, subnormal kidney function, reduced myocardial function, reduced energy expenditure, abnormal thyroid hormone metabolism, impaired psychosocial well-being, decreased lean body mass and decreased bone mineral content. Several studies have shown unanimously that GH replacement therapy in GH-deficient adults have improved all the above-reported clinical symptoms. We conclude that GH deficiency in adults is associated with a number of subnormal features. GH treatment improves (normalizes) these symptoms and we therefore believe that GH replacement therapy of a GH-deficient individual should be continued after cessation of linear growth. However, treatment of such patients should be carefully monitored since data from follow-up studies are still lacking.
GH replacement therapy in GH-deficient adults has recently been shown to increase (normalize) muscle volume and decrease adipose tissue volume as measured by means of CT scan and skinfold thickness. Also in adults with acquired GH deficiency in adulthood, GH replacement has been shown to significantly influence body composition with an increase in lean body mass and a reduction in skinfold thickness. Preliminary results from an open long-term trial indicate that 12 months of GH substitution result in a further normalization of the muscle/fat ratio. The fluid-retaining effect, with a significant increase in extracellular-fluid volume demonstrated during GH administration to normal subjects, seems to be of little clinical importance if a replacement dose around 2 IU/m2/day is chosen for young GH-deficient adults. Long-term trials are needed to finally establish the indication of GH replacement therapy in GH-deficient adults.
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A microspectrophotometric study of the DNA content of carcinoma-in-situ germ cells in the testes of eight infertile men revealed an aneuploid DNA distribution pattern. The results support the assumption that carcinoma-in-situ germ cells are of a malignant nature. The findings also indicate that the DNA content can be used to discriminate between carcinoma-in-situ germ cells and spermatogonia.
Testosterone tablets of crystal size 2-5 micrometer were administered orally for 10 dags to 3 human subjects with low endogenous serum testosterone (se-T) levels. Fifty mg testosterone increased se-T slightly, while one daily dose of 200 mg maintained the se-T level within normal range for men for more than 12h. No cumulative effect was seen. Seven further subjects with low androgen production ingested 100 or 200 mg testosterone of crystal size 125-400 micrometer. Blood samples were taken frequently during the 24 h period following administration of the testosterone and se-T levels determined. Testosterone levels in serum increased in 6 patients and was maintained within the normal male range for 5-7 h. In one subject a slight but significant increase in se-T was observed although the level did not reach the normal male range. Although it has been shown that it is possible to use orally administered testosterone to maintain se-T levels in the normal male range, the convenience to the patient must be balanced against the cost and possible side effects of the large doses required.
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