Abstract. The investigation of steroids in compartments of the genital tract of boars revealed that in the tubular fluid a pattern apparently exists which is unique in this compartment. It is characterized by high concentrations of unconjugated testosterone (35 ng/ml) and even higher amounts of oestradiol-17β (42.6 ng/ml) whereas in other compartments oestrone is the predominant oestrogen. At least in the ejaculate half of the total amount of oestrogens is bound to sperms and it is concluded that sperms act as a carrier for oestrogens. The accessory sex glands contribute to ejaculate concentrations to a varying degree (unconjugated testosterone 55%, conjugated testosterone 20%, unconjugated oestrogens 22%, conjugated oestrogens 12%) as could mainly be demonstrated by vasectomy with and without administration of hCG. Increasing the frequencies of ejaculations (up to three times a day) shows that the steroid transfer into the ejaculate is a rapid process.
R. Claus, D. Schopper and C. Hoang-Vu
C Schmutzler, C Hoang-Vu, B Ruger and J Kohrle
OBJECTIVE: Disturbed expression of retinoic acid (RA) receptors (RAR/RXR) contributes to the pathogenesis and tumor progression of epithelial carcinomas. DESIGN: To examine whether altered responses to retinoids may correlate with differences in RA receptor equipment, retinoid effects were examined in human thyroid carcinoma cell lines of various differentiation stages in culture and after xenotransplantation onto rodent models. METHODS: Cell growth was assessed by the MTT test, mRNA expression was examined by Northern blot and quantitative competitive RT-PCR, and type I 5'-deiodinase (5'DI) activity was measured by in vitro deiodination assay. Nude rats and mice were used for xenotransplantation experiments. RESULTS: All-trans-RA and RAR-selective synthetic retinoids stimulated activity and mRNA expression of the thyroid differentiation marker 5'DI in the follicular thyroid carcinoma cell line FTC-133. In the less differentiated FTC-238 cells, stimulation of 5'DI activity was less pronounced than in FTC-133 cells, and a reduced level of RAR beta mRNA was detected. In the anaplastic thyroid carcinoma cell lines HTh 74 and C 643, the activity of 5'DI was not increased by retinoids, and expression of RAR alpha mRNA was reduced. Proliferation of FTC-133 and FTC-238 cells was decreased by all-trans-RA. Pretreatment of FTC-133 with RA resulted in a reduced tumor growth in xenotransplantation experiments as compared with untreated control cells. This reduction was less pronounced in the case of FTC-238 cells. Thus, retinoid therapy might be applied to treat follicular thyroid carcinomas. However, tumor-specific RAR repertoires need to be analyzed as a prerequisite for successful intervention with appropriate, probably receptor-selective retinoids.
M Blaker, A de Weerth, M Tometten, M Schulz, W Hoppner, D Arlt, C Hoang-Vu, H Dralle, H Terpe, L Jonas and T von Schrenck
OBJECTIVE: The cholecystokinin(2)-receptor (CCK(2)R) promotes secretion and cell growth induced by its ligands cholecystokinin (CCK) and gastrin. The receptor has recently been shown to be expressed in human medullary thyroid carcinomas (MTCs). The objective of this study was to analyze CCK(2)R expression in MTC samples of different tumor stages as well as in non-malignant thyroid tissues. DESIGN AND METHODS: Using RT-PCR we investigated 19 MTC samples and TT-cells (a human MTC cell line), as well as samples of normal thyroid. In addition, we performed immunohistochemistry using calcitonin- and CCK(2)R-specific antibodies on MTCs and samples of C-cell hyperplasia. RESULTS: We demonstrate for the first time that CCK(2)R is expressed not only in MTCs but in all samples of normal thyroid tissue. Using immunohistochemistry the receptor could be localized on calcitonin-secreting C-cells. The highest incidence of CCK(2)R expression in MTCs was observed in early-tumor stages, whereas CCK(2)R could not be detected in advanced or metastasized tumors. CONCLUSIONS: The expression of CCK(2)R in C-cells suggests a physiological function for gastrin and/or CCK in the regulation of calcitonin release, presumably related to bone and calcium metabolism. Moreover, these ligands might act as growth factors in MTCs. Efforts in the development of CCK(2)R scintigraphy for the detection of MTC lesions might have to consider a lower incidence of the receptor in advanced tumor stages.