TIME-DEPENDENT DECREASE OF PITUITARY RESPONSE TO LH-RH AFTER CHRONIC TREATMENT OF INTACT FEMALE RATS WITH ETHINYLOESTRADIOL AND NORETHINDRONE

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.

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.


1975 ◽  
Vol 66 (1) ◽  
pp. 13-20 ◽  
Author(s):  
D. C. JOHNSON ◽  
R. S. MALLAMPATI

SUMMARY Release of immunoreactive LH and FSH was induced in immature intact female rats by repeated injections of synthetic luteinizing hormone releasing hormone (LH-RH). Altering the dose of LH-RH (5, 10, 20, 50 ng) and the frequency of administration (every 10, 20, 30 or 60 min) over a period of 2 h produced a variety of serum LH and FSH concentrations and ratios. When the dose was a constant 20 ng but the frequency of injections was either 20 or 30 min, a steady state in serum gonadotrophin concentrations was reached within 1 h and the level remained the same during the second hour. When given every 10 min, 20 ng LH-RH produced a much higher concentration of both LH and FSH during the second hour of stimulation. Examination of the gonadotrophin levels after each injection of LH-RH showed that the pituitary response was variable in spite of a constant stimulus.


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.


1981 ◽  
Vol 240 (3) ◽  
pp. E297-E301
Author(s):  
L. K. Tang ◽  
F. Y. Tang

Effects of 17 beta-estradiol (E2) on adenosine 3',5'-cyclic monophosphate (cAMP) binding and luteinizing hormone (LH) and prolactin (PRL) responses to N6-O-2'-dibutyryl cAMP (DBcAMP) were examined in pituitary monolayer cultures prepared from female rats. Incubation with 8 mM DBcAMP for 4 h significantly (P less than 0.05) increased both LH and PRL release into medium by two- to threefold. E2 pretreatment augmented the DBcAMP-induced LH release but not PRL release to 160% of the non-E2-treated controls. However, the cellular and total accumulation of both LH and PRL were significantly increased in cultures pretreated with E2. The effect of E2 was time dependent, and the maximal effect was observed after 3 days of treatment. Furthermore, E2 treatment significantly increased cAMP-binding activities to 254% of the non-E2-treated controls. The time course of the E2 effect on cAMP-binding activities closely resembled the time course of the E2 effect on LH and PRL accumulation as well as the DBcAMP-induced LH release. These results suggest that the priming effect of E2 on pituitary LH and PRL responses to DBcAMP is associated with increased hormone synthesis and cAMP binding stimulated by E2 pretreatment.


1975 ◽  
Vol 67 (3) ◽  
pp. 359-369 ◽  
Author(s):  
SUSAN C. WILSON ◽  
P. J. SHARP

SUMMARY Single intramuscular injections of 0·5 mg progesterone/kg resulted in increased LH secretion in laying hens but not in pullets with completely undeveloped sexual organs. Injections of the steroid were first able to stimulate LH release 8–10 weeks before the onset of lay when the comb, ovary and oviduct had started to grow and basal plasma LH concentrations were beginning to rise. At this time, injections of 10 μg synthetic LH-RH/kg resulted in an incremental change in plasma LH levels of around 26 ng/ml. A similar incremental change was observed after giving the same dose of LH-RH to pullets with no signs of sexual development. Three to four weeks before the first eggs were laid, basal plasma LH levels started to fall, the pituitary became progressively more insensitive to synthetic LH-RH and injections of 0·5 mg progesterone/kg resulted in a reduced LH response. Ten μg LH-RH/kg caused incremental changes in blood levels of LH of less than 5 ng/ml. The final stage of sexual maturation occurred during the week before the onset of lay and was characterized by a rapid growth of large yolky ovarian follicles and a further fall in the sensitivity of the pituitary to synthetic LH-RH. However, injections of 0·5 mg progesterone/kg resulted in a prolonged release of LH. These observations are discussed in relation to the maturation of the positive feedback mechanism by which progesterone stimulates the secretion of LH.


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

1977 ◽  
Vol 84 (1) ◽  
pp. 62-71 ◽  
Author(s):  
W. Beck ◽  
S. Engelbart ◽  
M. Gelato ◽  
W. Wuttke

ABSTRACT High serum prolactin levels were induced in chronically castrated female rats by pituitary transplants from male donor rats. The typical pulsatile LH release pattern observed in castrated control rats was maintained in pituitary grafted rats, when pituitary transplantation was performed simultaneously with castration 3 months before withdrawal of the blood samples. If pituitaries were transplanted into chronically castrated rats and blood samples were withdrawn 3 days later, the pulsatile LH release was abolished and basal or moderately elevated LH levels were found. Chronically or subacutely elevated prolactin levels had no effect on high serum FSH values. Pituitary transplants into intact female rats at day 23 after birth also suppressed basal LH values for 4 days without alterating the serum FSH levels. Six and 8 days after transplantation the serum LH levels were normal. Pituitary transplantation into these immature rats advanced puberty by more than one week. These results indicate that prolactin has an antigonadotrophic effect in female rats which is directed only towards pituitary LH but not FSH secretion. The inhibitory action of high serum prolactin levels on pituitary LH release does not last longer than 4–6 days under steady state conditions, such as found in the constantly high prolactin levels due to pituitary transplants. Under natural conditions with steadily increasing prolactin levels between day 20 and puberty the effect of prolactin in inhibiting pituitary LH release may last longer. Thus, prolactin may be one of the, if not the regulator of the timing of puberty.


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