THE ACTIVITY OF AN LH-RH-DEGRADING ENZYME IN THE ANTERIOR PITUITARY DURING THE RAT OESTRUS CYCLE AND ITS ALTERATION BY INJECTIONS OF SEX HORMONES

1978 ◽  
Vol 87 (3) ◽  
pp. 476-484 ◽  
Author(s):  
Herbert Kuhl ◽  
Christian Rosniatowski ◽  
Hans-Dieter Taubert

ABSTRACT The basal activity of an LH-RH-degrading enzyme system, L-cystine arylamidase, was determined in the pituitary gland of female rats at 4 h intervals throughout the 4-day oestrus cycle. The activity of the enzyme was found to be fluctuating during the four stages of the cycle in a circadian rhythm with the highest values occurring at night and the lowest values at noon. The maximal activity for the whole cycle was measured at 04.00 h on the day of metoestrus, and the minimal activity between 12.00 h and 16.00 h on the day of pro-oestrus. The iv injection of various doses of oestradiol caused only a slight change in enzyme activity of the pituitary during oestrus, but considerable increases were observed during the other three stages. The stimulation of enzyme activity by progesterone was much more pronounced during dioestrus and pro-oestrus as compared with metoestrus and oestrus. Similarly the reaction to the injection with LH and prostaglandin E2, repectively, were not very pronounced during oestrus and metoestrus, whereas the enzyme activity rose by +50% and +100%, respectively, during dioestrus and pro-oestrus. The LH-RH-degrading enzyme system in the pituitary seems to be involved in the control of the tonic LH release, and in the maintenance and regulation of the sensitivity of the gonadotrophs to alterations in LH-RH release from the median eminence.

1978 ◽  
Vol 89 (2) ◽  
pp. 240-250 ◽  
Author(s):  
Herbert Kuhl ◽  
Angelika Sachs ◽  
Christian Rosniatowski ◽  
Hans-Dieter Taubert

ABSTRACT The effect of daily injections of 50 μg ethinyloestradiol and 1 mg norethindrone upon basal and LH-RH-stimulated LH release was investigated in intact adult female rats during a period of 30 days. Basal plasma LH was depressed by about 30 % during the whole time of steroid treatment, and returned to the level of the control values two weeks after discontinuation. The injection of 30 ng and 150 ng LH-RH into untreated rats resulted in a significant increase of plasma LH which was, however, not dose-dependent. After the treatment with ethinyloestradiol and norethindrone for 5 days, the pituitary response to 150 ng was approximately four times higher than that to 30 ng. The LH release after injection of 150 ng LH-RH decreased significantly with the duration of steroid treatment, and was totally abolished by 30 days; whereas two weeks after the termination of steroid application the pituitary responded to LH-RH in the same manner as in control rats. When 30 ng LH-RH were injected into oestrogen/norethindrone treated rats, no decrease in LH release was found until day 20 of the experiment. By 30 days of treatment no rise in plasma LH could be elicited. The activity of the LH-RH-degrading enzyme L-cystine arylamidase was stimulated during the treatment with ethinyloestradiol and norethindrone in the pituitary by approximately 100 %, whereas almost no effect on this enzyme was seen in the hypothalamus. It is concluded that the chronic treatment of intact female rats with ethinyloestradiol and norethindrone causes time-dependent and reversible alterations in the storage of LH in the pituitary. The elevated activity of the LH-RH-degrading enzyme in the pituitary is possibly involved in these processes and/or in the mechanism responsible for the depression of basal LH.


1977 ◽  
Vol 86 (1) ◽  
pp. 60-70 ◽  
Author(s):  
Herbert Kuhl ◽  
Christian Rosniatowski ◽  
Hans-Dieter Taubert

ABSTRACT It had previously been shown that a luteinizing hormone-releasing hormone (LH-RH)-inactivating enzyme in the rat hypothalamus, L-cystine arylamidase, is in all probability involved in the short-loop feedback mechanism of LH. Since this enzyme system was also shown to be present in the pituitary, the effect of the iv injection of several sex hormones upon its activity was investigated. The basal arylamidase activity was found to be considerably higher in the neurohypophysis as compared to the adenohypophysis. The injection of 10 μg LH brought about a significant rise in arylamidase activity (+60 %) only in the latter. There was a dose-dependent increase in the pituitary enzyme activity 2 h after the iv administration of LH, and 16 h after the injection of oestradiol and progesterone into dioestrous rats. Contrary to previous findings obtained with hypothalamic homogenates, the effect of LH upon the enzyme in the pituitary proved to be not dependent on the presence of sex steroids, as the iv application of 10 μg LH into ovariectomized rats resulted in an increase of pituitary L-cystine arylamidase by about 30 %. The injection of testosterone, oestradiol and - to a lesser degree - progesterone into adult male rats caused a significant increase of enzyme activity in the hypophysis. Progesterone proved to be ineffective in the hypothalamus. This indicates that in contrast to the hypothalamus there is no sex-specific response of the LH-RH-degrading enzyme in the pituitary. It is concluded that this enzyme system seems to play an important part in the mechanisms regulating gonadotrophin release in the pituitary.


1986 ◽  
Vol 14 (03n04) ◽  
pp. 157-160 ◽  
Author(s):  
Akira Miyake ◽  
Jin-Woo Lee ◽  
Keiichi Tasaka ◽  
Shirou Ohtsuka ◽  
Toshihiro Aono

For examination of the effect on luteinizing hormone (LH) release of Wen-Jing-Tang, a traditional Chinese herbal medicine, the pituitary from normal female rats in diestrus was perifused alone or in sequence with the mediobasal hypothalamus (MBH) in a sequential double-chamber perifusion system. Wen-Jing-Tang at 5 or 500 μg/ml induced significant LH release (60-95 % increase) from the pituitary in series with the MBH, but had no effect on LH release from the pituitary perifused alone. These data suggest that Wen-Jing-Tang induces LH release from the pituitary through hypothalamic LH-RH.


1979 ◽  
Vol 92 (4) ◽  
pp. 648-657 ◽  
Author(s):  
J. de Koning ◽  
J. A. M. J. van Dieten ◽  
A. M. I. Tijssen ◽  
G. P. van Rees

ABSTRACT The hypothesis that LH-RH induces LH release partly through a protein synthesis dependent step (protein factor) was further investigated using two different experimental designs. First, during incubation of pituitary glands of intact dioestrous female rats with a maximally active concentration of LH-RH, the inhibitor of protein synthesis cycloheximide was added at various times after the beginning of the incubation. The results show that it takes a relatively long time, i.e. more than 1 h of exposure to LH-RH before the amount of the protein factor has increased sufficiently to allow a maximal LH secretion. Secondly, LH-RH was injected iv after which the protein factor was assayed by incubating the pituitary glands with a maximally active concentration of LH-RH in the presence of cycloheximide and measuring LH release in vitro. It was found that 1 h after the injection sufficient protein factor was present to permit an elevated response to LH-RH. This response could be suppressed by injecting cycloheximide prior to LH-RH. When the interval between injection of LH-RH and beginning of the incubation was increased to 2 h, LH release in vitro decreased again. However, ovariectomy immediately before LH-RH injection resulted in maintenance of the elevated response to LH-RH in vitro, indicating a role of the ovaries in this phenomenon.


1981 ◽  
Vol 88 (3) ◽  
pp. 329-338 ◽  
Author(s):  
J. DE KONING ◽  
J. A. M. J. VAN DIETEN ◽  
A. M. I. TIJSSEN ◽  
G. P. VAN REES

The involvement of cyclic AMP in the action of LH releasing hormone (LH-RH) on LH secretion was studied by incubating pituitary glands from adult female rats on day 2 of dioestrus with 1 mm-N6-monobutyryl cyclic AMP (mbcAMP) and 10 mm-theophylline for periods of up to 10 h. This treatment induced a pattern of LH release similar to that observed in the presence of a low concentration of LH-RH (0·1 ng LH-RH/ml), i.e. an initial 4 h period during which the release of LH was minimal was followed subsequently by an increased rate of release. In this system inhibition of protein synthesis by cycloheximide (25 μg/ml) did not impair the initial response of the pituitary tissue but the increase in the rate of LH release during the second phase of the response was blocked. Preincubation with mbcAMP and theophylline increased the responsiveness of the pituitary tissue to LH-RH. This action could be prevented by including cycloheximide during the preincubation period, whereas addition of this drug during the incubation with LH-RH no longer impaired the increased responsiveness. The size of the sensitizing action of mbcAMP and theophylline mediated through the induction of protein synthesis was comparable with that of a high concentration of LH-RH. From the absence of a significant change in total LH during the preincubation period, it was concluded that the increased responsiveness was not the result of newly synthesized LH. The present results suggest a role or roles for cyclic AMP in the secretion of LH induced by LH-RH. Besides an effect on the formation of a factor related to the synthesis of protein, other than LH which has a permissive role in the acute release of LH, cyclic AMP might also be concerned in the secretion process through a pathway which does not involve synthesis of protein.


1983 ◽  
Vol 98 (1) ◽  
pp. 47-53 ◽  
Author(s):  
Y. S. Bakhle ◽  
J. T. Zakrzewski

The metabolism of prostaglandin E2 (PGE2) in lungs from female rats was measured during the stages of the oestrous cycle. In isolated lungs perfused through the pulmonary circulation, only 7–20% of PGE2 escaped metabolism, as measured by bioassay and radioimmunoassay. Within these limits, survival was highest at pro-oestrus compared with metoestrus and dioestrus. Uptake of PGE2 from the pulmonary vasculature, assessed by measuring the efflux of radioactivity derived from [14C]PGE2 injected into the pulmonary circulation of the isolated lung, did not show cycle-related variations. Assay of [14C]PGE2 metabolism by tissue homogenates prepared from lungs taken at different stages of the oestrous cycle showed a significant decrease in enzyme activity at pro-oestrus compared with dioestrus. It is concluded that PGE2 metabolism in isolated rat lung is affected by the oestrous cycle and that the increased PGE2 survival at pro-oestrus may be more readily explained by changes in enzyme activity than by changes in uptake of substrate.


1975 ◽  
Vol 78 (4) ◽  
pp. 649-663 ◽  
Author(s):  
Herbert Kuhl ◽  
Hans-Dieter Taubert

ABSTRACT The effect of the intravenous administration of several hormones on L-cystine arylamidase in the hypothalamus of the rat was examined. The injection of 10 μg LH into adult male and female rats was followed within 90 min by an increase of the enzyme activity by 50 %, while infantile animals were not affected. When prepuberal rats were pre-treated sc with testosterone and oestrogen respectively, the iv injection of LH brought about a rise in hypothalamic arylamidase activity. When ovariectomized rats were tested, no response was seen after LH injection unless the animals had been pre-treated with oestrogen and progesterone. The iv injection of 0.1 μg oestradiol-17β into female, and of 0.5 μg testosterone into male intact mature rats also resulted in an increase of hypothalamic enzyme activity. The maximal increase in enzyme activity was seen 16 h after steroid treatment. As it had previously been shown that L-cystine arylamidase inactivates LH-RH, it may be assumed that this enzyme is involved in the short-loop feedback of LH. This assumption is based on the observation that an elevation of plasma LH brings about an activation of the enzyme system, which subsequently leads to increased inactivation of LH-RH in the hypothalamus. This mechanism seems to depend on the presence of certain plasma levels of oestrogen in female, and of testosterone in male animals.


Life Sciences ◽  
1984 ◽  
Vol 34 (20) ◽  
pp. 1937-1943 ◽  
Author(s):  
J. de Koning ◽  
A.M.I. Tijssen ◽  
T.R. Koiter ◽  
G.A. Schuiling ◽  
G.P. van Rees

Author(s):  
Choudhuri D. ◽  
Bhattacharjee T.

Background : Toxicological consequences arising from exposure to mixtures of heavy metals especially at low, chronic and environmentally relevant doses are poorly recognised. In the present study, we evaluated effects of chronic exposure to combinations of three metals arsenic (As), cadmium (Cd) and lead (Pb) present frequently in drinking water on reproductive function and oxidative damage caused to reproductive organs of female rats. Method : Female rats were exposed to mixture of metals (As, Cdand Pb) for 90 consecutive days. The gain in body weight and weight of reproductive organs were recorded following autopsy on 91 stday. The oestrus cycle were monitored during entire treatment period. Numbers of corpora lutea, implantation sites, live fetus and survival of the fetus were evaluated in rats mated successfully with untreated male after completion of their respective treatment. Ovarian cholesterol, protein, ascorbic acid and enzyme Δ 5 -3β HSD levels were estimated. Serum levels of steroid hormones oestrogen and progesterone were estimated. Histopathological picture of both ovary and uterus were assessed. Levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidise (GPX) activity, amount of reduced glutathione (GSH) and malondyaldehyde (MDA) in blood, ovary and uterus were measured as biomarkers of oxidative stress. Results : The treated rats showed reduced body weight gain and reduction in the weight of ovary and uterus. Oestrus cycle was disrupted with continuous diestrous in treated animals. Number of corpora lutea, implantation sites and live fetus and the survival of fetus evaluate were reduced significantly in treated groups. The levels of ovarian cholesterol and ascorbic acid increased in treated rats with decrease Δ5 -3β HSD level. There was reduction in serum level of both the ovarian steroid hormones oestrogen and progesterone. The protein levels did not differ between the groups. There was a significant increase in levels of MDA and decrease in levels of all the antioxidant enzymes in treated group. Conclusion : The results revealed there was disruption to reproductive functions with decrease in stereoidogenic activity and associated oxidative stress in female rats treated with combination of mixture of metals (Cd, As and Pb) at low dose for 90 consecutive days.


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