Effect of local epididymal levonorgestrel on the fertilizing ability of male rat, a model for post-testicular contraception.

A thin levonorgestrel-silicone layer was applied on the capsule of the cauda epididymis of male rats to study a model for post-testicular male contraception. The effect of different levonorgestrel doses on the fertility of males was tested with fertile females. The time-dependent influence of a standard dose of levonorgestrel on serum LH and on testicular histology was estimated. Among the males tested, there was a group of animals where successful contraception with local application of levonorgestrel-silicone membrane was obtained. Sexual behavior was normal and the spermatogenesis was functioning, but the sperm were infertile. Although further research is needed to estimate adequate dose and strength of levonorgestrel in silicone matrix, this study shows that post-testicular contraception is possible to achieve.

Aryl hydrocarbon hydroxylase activity in spontaneous mammary tumors in rat.

The development of spontaneous mammary tumors was observed for about 2 years in a group of 25 female Sprague-Dawley rats aged over 1 year at the beginning of the study. All younger females in our animal facility were similarly monitored. In old females, the incidence of spontaneous mammary tumors was 64%. The parity of rats did not protect them from tumorigenesis, but the proportion of malignant tumors was higher in virgin (57%) than in parous (13%) rats. Activities of cytochrome P450IA1-dependent enzyme (aryl hydrocarbon hydroxylase, AHH) and NADPH-cytochrome P450 reductase (NCR) were determined in microsome fractions isolated from livers, lungs, uteri and tumors of rats. AHH and NCR activities in tumors and uteri were low compared to those in livers or lungs. In tumors, the activity distributions were wide, even in different tumors of the same animal the AHH activities varied as widely as between different animals. The activities in benign and malignant tumors were not statistically significantly different. No correlation with liver, lung or uterine activities was found either. With ageing of the rat, the AHH activities in tumors, liver and lungs decreased. The behavior of AHH in spontaneous mammary tumors in rats seems to be similar to that found in chemically induced tumors and seems to show individual regulation, possibly altered by tumorigenesis in each individual tumor.

Aryl hydrocarbon hydroxylase activity in chemically induced and toremifene-treated mammary tumors in rats.

Aryl hydrocarbon hydroxylase (AHH) and NADPH-cytochrome P450 reductase (NCR) activity of microsomes from liver, lungs, uterus and mammary tumors in dimethylbenzanthracene-induced and toremifene-treated female Sprague-Dawley rats were studied. AHH and NCR activity in tumors and uteri was low compared with that in livers and lungs. The distribution of AHH in tumors was wide and skewed. It varied in different tumors of the same animal as widely as between different animals. The enzyme activity in tumors did not correlate with that in the liver, lungs or uterus of the same animal. Toremifene had no effect on AHH or NCR in tumor or liver, but it decreased them in lungs. Tumor AHH activity correlated with its overall growth rate and development stage. The results suggest that malignant transformation leading to the defect in growth regulation also confuses the complex regulatory system of AHH activity.

Low serum progesterone levels and tubal dysfunction--a possible cause of ectopic pregnancy.

We analyzed 22 human oviducts by the suction electrode method for electrical activity (preceding and reflecting the mechanical activity), as related to serum progesterone levels. Eleven patients had high progesterone levels (greater than or equal to 20 nmol/L), but the other 11 patients had low levels. When the serum progesterone level was low, the oviductal electrophysiologic characteristics were those associated with poor ovum transfer: low probability of prouterine propagation of the activity at the fimbrial end of the tube: high-frequency but low number of electrical bursts, reflecting possible weak propulsive force; and a high occurrence rate of sine-wave-like activity and inactive areas where ovum retention can occur. These phenomena could be related to the higher incidence of ectopic pregnancies in patients with luteal phase defect.

Somatostatin concentrations in discrete hypothalamic nuclei of genetically obese Zucker rats.

Hypothalamic somatostatin concentration was determined in 6.5 to 9 months old male and female genetically obese fatty (fa/fa) and lean (Fa/-) Zucker rats. Similar somatostatin levels were found in fatty and lean animals in the hypothalamic regions previously known to contain the highest hormone levels (median eminence and arcuate, periventricular and ventromedial nuclei). The fatty animals were grossly obese and had a pronounced hyperinsulinemia.

Experimental Yersinia-associated arthritis in the spontaneously hypertensive rat.

Sterile arthritis resembling human reactive arthritis was induced in spontaneously hypertensive SHR rats by intravenous injection of live Yersinia enterocolitica 0:8. Histologically the synovitis appears as proliferation of the lining cell layer, with inflammatory cells present in the subsynovium. The inflammatory cells are mostly lymphocytes. Infection with Yersinia enterocolitica 0:3 or Yersinia pseudotuberculosis did not induce arthritis. Susceptibility to Yersinia-associated arthritis is not determined by the major histocompatibility complex (MHC), since rats of the normotensive control strain (WKY) with the same MHC do not develop arthritis.

Yersinia-associated arthritis in the rat: experimental model for human reactive arthritis?

Rats of five different strains were injected intravenously with live Yersinia enterocolitica O:8 or Yersinia pseudotuberculosis III. Twelve to 18 days after inoculation of Y. enterocolitica O:8, arthritic symptoms appeared in the hindpaws of SHR rats. They started with erythema, followed by swelling and painful movement, closely resembling findings in adjuvant arthritis. Histologically, the inflammation was dominated by neutrophils in two cases, whereas in two others the inflammatory cells were predominantly lymphocytes. Two of five rats yielded positive bacterial cultures from the joints. Altogether, arthritis was observed in five of nine SHR surviving beyond day 14 after the bacterial inoculation. Rats of Lewis, Wistar, WKY and Zucker strains did not develop any signs of arthritis after intravenous injection of Y. enterocolitica or pseudotuberculosis. Also in the SHR rats, Y. pseudotuberculosis failed to induce arthritis.

Regional variations in transport of the luminal contents of the rat epididymis in vivo.

The speed of transport of the luminal contents of the epididymis was studied by injecting small droplets of stained paraffin oil into the lumen in 10 different regions of the epididymal duct of 64 anaesthetized rats and measuring the distances the droplets moved in 2 h. The oil droplets became dispersed, and there was much variation between the animals. The dispersion distances were longest in the proximal caput and shortest in the corpus. The distributions of the transport distances of the oil droplets were discontinuous and multimodal in the proximal caput, and bimodal in the cauda. The transport speed decreased steeply from 420 mm/2 h in the most proximal caput to 64.2 mm/2 h in the beginning of the distal caput. In the rest of the caput, corpus and cauda, speed was quite similar although it declined slightly towards the ductus deferens, being 25.5 mm/2 h in the most distal region of the cauda.

Movements of the luminal contents in two different regions of the caput epididymidis of the rat in vitro.

Transport of the epididymal contents was studied in vitro by filming, for 1-2.5 h, the movements of tiny, stained oil droplets injected through a micropipette into two regions of the lumen of the caput epididymidis: the most proximal part, with the widest outer diameter (region I), and the neighbouring, narrowest portion (region II). The movements of the oil droplets were pendular. Displacement, caused by a contraction of the wall spreading in either direction, was followed by a shorter, usually passive reflux leading to a small net displacement, delta l. The distance of transport during 5 min periods varied between 0.09 and 16.79 mm (median 1.0 mm) in region I and 0.05 and 3.62 mm (median 0.42 mm) in region II. Transport divided into periods when little or no net transport took place (slow transport) and periods when the transport was effective (fast transport). Although the periods of fast transport were infrequent, their significance in transport towards the ductus deferens was high. During 5 min sampling periods of fast transport, the pendular movements were longer in both regions: delta l was longer in region I and the probability of delta l being in the direction of transport was higher than during slow transport in both regions. The mean probability of delta l being in the direction of the ductus deferens was 0.63 in region I and 0.57 in region II. Higher frequency of pendular movements, longer delta l values and higher probability of delta l being towards the ductus deferens in region I than II suggest that the transport speed is higher in region I than II. Transport consisting of short steps occurring with variable probabilities in both directions is a stochastic process.

Relation of electrical activity to luminal transport in the cauda epididymidis of the rat in vitro.

Droplets of stained paraffin oil were injected into the lumen of the rat cauda epididymidis through a microcapillary in vitro at a mean distance of 36 /+- 8 cm from the beginning of the ductus deferens. The location of a droplet was marked on a 6-channel recorder graph after each event of electrical activity of the wall musculature. Transport of the droplets consisted of pendular movements. The droplet moved in the direction of the spread of electrical activity then returned almost to its original position during reflux. The net distance for transport was dependent on the direction of the spread of activity and on the percentage of the non-propagating activity. The mean probability for the spread of the electrical activity towards the ductus deferens between the pairs of the electrodes was 0.54 and the mean net transport was 6.2 /+- 1.8 )s.e.m.) mm/h, towards the ductus deferens in 7 out of 10 ducts.

Effects of oxytocin and vasopressin on electrical and mechanical activity of the rat epididymis in vitro.

Electrical and mechanical activity of the caput and cauda epididymidis were recorded at measured distances from the beginning and end of the epididymal duct. Oxytocin had no significant effects on the caput on cauda. Vasopressin increased significantly the frequency of the electrical activity in the caput and cauda and frequency of contractions and basal tension of the cauda at a dose of 4 X 10(-1) mU/ml and even more at a dose of 4 mU/ml. The maximal increase in frequency of activity was 70-90% in the cauda and about 35% in the caput.

Spontaneous electrical activity of the rat epididymis in vitro.

Smooth muscle electrical activity was recorded with suction electrodes from the partly or completely uncoiled epididymal duct of the rat in vitro. The electrical activity of the cauda epididymidis consisted of one or few spikes followed by a plateau of 1-2 sec. The frequency of electrical activity declined from the thicker-walled initial segment of the thin-walled initial segment, was increased to the level seen in the initial segment in the thicker, major portion of the caput epididymidis, declined in the corpus and fell steeply in the cauda epididymidis towards the vas deferens. Electrical activity spread over long distances in the distal cauda and epididymal vas. Elsewhere in the epididymis activity remained synchronous only for a short period in short segments.