Summary. In adult male rats treated with streptozotocin 6weeks before the experiments, androgen-binding protein concentration was increased in testicular tissue by 33% (p< 0.01) and reduced in epididymal tissue by 25% (p < 0.005) in animals exhibiting severe hyperglycaemia as compared with animals remaining in normoglycaemia or moderate hyperglycaemia. Androgen-binding protein content was diminished in epididymal tissue by 40% (p< 0.0005) but not changed in testicular tissue. If related to constant body weight, the sum of testicular and epididymal androgen-binding protein was identical in both norrno-and hyperglycaemic animals. This disturbance in androgen-binding protein distribution may be the consequence of altered testicular secretion or impaired transport of androgen-binding protein from testes to epididymides. Numerous studies have demonstrated impairment of fertility [1] and testicular endocrine function [1-4] to be late complications of streptozotocin-treated hypoinsulinaemic, hyperglycaemic male rats. In addition to reports on defective spermatogenesis [5][6] and indications of disturbances of pituitary gonadotropin secretion [1][2][3][5][6][7], dysfunction of the Leydig cells resulting in diminished testosterone formation in these diabetic animals seems to be the most extensively investigated problem in this field [1][2][3][4]. Key words:In contrast, less attention has been drawn to Sertoli cell function in diabetic animals. Although a specific androgen-binding protein (ABP) was shown several years ago to be a marker of Sertoli cell function [8][9][10][11][12][13], ABP measurements in diabetic rats have been reported in only one study [2]. A paradoxical increase of ABP content (expressed as lxl-equivalent of epididymal cytosol standard) of the testes (the site of production) but no change of ABP content of the epididymis (a possible site of action) has been found in rats 4 weeks after streptozotocin injection [2].The aims of the present study on streptozotocintreated male rats were to re-evaluate those results, to distinguish between ABP concentrations and ABP content of testes and epididymides by consideration of changes in organ weights and to make correlations between testicular or epididymal ABP and blood glucose levels in order to prove possible diabetes-induced changes in testicular ABP secretion. Materials and methodsEighteen male Han: Wistar rats, weighing 214 + 5 g (mean + SEM) at the beginning of the study, received 65 mg streptozotocin (2-desoxy-2-(3-methyl-3-nitrosurea)-la-glucopyranose; Calbiochem, Giel3en, FRG)/kg body weight, i.p. (experimental group). One rat died during week 3. Five animals (205 ___ 5 g initial body weight) were injected with citrate buffer only and served as a control group. All animals were allowed food (Altromin 1314; Altromin, Lage, FRG) and tap water ad libitum.Post-prandial blood glucose levels were examined routinely (seven times during the 6-week period of the experiment) using the Eyetone reflectometer system (Dextrostix; Ames-Miles, Frankfurt/Main, FRG). Urin...

Summary.In streptozotocin-treated adult male rats, the mechanisms of reduced response of testicular Leydig cells in vitro to stimulation with human chorionic gonadotropin was investigated. A decrease in testosterone formation by 70% after 6 weeks of diabetes mellitus is combined with diminished intracellular cyclic AMP accumulation as well as with a disturbance in progesterone conversion to androgens. The latter is also reflected by reduced progesterone binding to the cytochrome P-450 moiety of the steroid-17a-hydroxylase system.Key words: Streptozotocin-diabetes, Leydig cells, human chorionic gonadotropin, cyclic AMP, testosterone production, steroid metabolism, progesterone binding to cytochrome P-450.Disturbances of spermatogenesis are well-known complications of diabetes mellitus in male patients, but there are only few and contradictory data concerning their hormonal state [1].Streptozotocin-induced diabetes mettitus in rats is frequently used as a model for studying late effects of the diabetic state. Among other complications, impairment of testicular function and fertility occurs in these diabetic animals: a spermatogenic arrest at step 7 spermatids was seen similar to that found in hypophysectomized animals [2]. Diminution of testicular androgen production in vivo as well as in vitro (incubation of interstitial cells) was described for streptozotocin-diabetic rats [3,4]. This depression of endocrine testicular function was reported to be the consequence of the small amounts of luteinizing hormone releasing hormone (LHRH) secreted by the hypothalamus and of a reduction of blood lutropin (LH) levels [3]. Testicular functions and fertility could be improved by insulin treatment [4] and restored by means of a combined insulinhuman chorionic gonadotropin (HCG) therapy [5].The present study was undertaken to answer the question (1) can the probable loss of LH receptors on the surface of Leydig cells [6] alone explain diminished testosterone synthesis in testes from streptozotocindiabetic rats ? (2) are there additional disturbances within the steroidogenic pathways which could also be responsible for diabetic testicular injury? Materials and MethodsMale Wistar rats, weighing 190-210 g at the beginning of the experiment, were used. Diabetes was induced by intraperitoneal injection of 100 mg streptozotocin/kg body weight (Calbiochem, GieBen, FRG; freshly prepared in 0.01 mol/l citrate buffer, pH 4.5). The diabetic state was verified by glucosuria 24 h later; venous blood levels of glucose were controlled at least twice weekly using the Ames reflectometer system. Animals exhibiting post prandial blood glucose levels < 3 g/1 were excluded from the diabetic group. In all other cases, duration of diabetes was 3 or 6 weeks as indicated. Control rats were given vehicle injection only. Animals were fed pelleted food and tap water ad libitum.With this dose of streptozotocin, a 95% manifestation rate of hyperglycemia and glucosuria was achieved; mortality rate was 8% (n = 43). The body weight gain was + 1% in diabetic a...

A complete dynamic analysis of cytochrome P-450(C-17)-catalysed androgen biosynthesis from a single dose of progesterone and 17 alpha-hydroxyprogesterone in a double-label double-substrate experiment was performed in order to elucidate the controversial intermediacy of 17 alpha-hydroxyprogesterone. Label distribution within the steroid fractions as well as in the membrane and buffer compartments yields direct evidence that the endogenously formed 17 alpha-hydroxyprogesterone (which is in an 'intermediate state') accumulates to a higher degree in microsomal membranes than does the exogenously added 17 alpha-hydroxyprogesterone (which is in a 'substrate state') under certain conditions. It is also demonstrated that endogenously formed 17 alpha-hydroxyprogesterone may partly leave the membrane compartment (in terms of a 'leakage' or 'overflow' phenomenon) and is then able to equilibrate with the pool of exogenously added 17 alpha-hydroxyprogesterone. Since only the label distribution in the membrane-associated (but not always in the aqueous) 17 alpha-hydroxyprogesterone pool corresponds to the label distribution in the androgen fraction, it is concluded that only the membrane-associated 17 alpha-hydroxyprogesterone pool is directly accessible to cytochrome P-450(C-17)-catalysed conversion into androgens.

The objective of the present study was to investigate the regulation of a key component of testicular androgen biosynthesis, i.e. the cytochrome P450XVII of the steroid-17 alpha-monooxygenase/C17,20-lyase, after surgical induction of bilateral cryptorchidism in vivo. Seven days after induction of cryptorchidism, P450XVII concentrations are diminished (as compared to sham-operated controls) by 64% in isolated purified Leydig cells but only by 44% in the total Leydig cell compartment of the testis, since the Leydig cell yield from cryptorchid testes is by 53% higher than that from control testes. Using microsomal suspensions prepared from testicular homogenates, P450XVII content per testis equivalent is found to be decreased by 36% seven days after incubation of cryptorchidism, whereas the P450XVII concentration per gram testis is not changed due to testicular involution. Fourteen days after induction of cryptorchidism, the induction of the Leydig cell system appears to superimpose on the down-regulation of P450XVII. The study demonstrates both a strong sensitivity of P450XVII to short-term elevation of testicular temperature and a differentiation between effects of cryptorchidism on total testicular content and specific cellular and subcellular concentration of this steroidogenic protein.

No abstract