THE REGULATORY FUNCTION OF A PITUITARY LH-RH-DEGRADING ENZYME SYSTEM IN THE FEEDBACK CONTROL OF GONADOTROPHINS

1977 ◽  
Vol 86 (1) ◽  
pp. 60-70 ◽  
Author(s):  
Herbert Kuhl ◽  
Christian Rosniatowski ◽  
Hans-Dieter Taubert
Keyword(s):  
Enzyme Activity ◽  
Enzyme System ◽  
Significant Rise ◽  
Male Rats ◽  
Ovariectomized Rats ◽  
Regulatory Function ◽  
Specific Response ◽  
Degrading Enzyme ◽  
Lh Rh ◽  
Cystine Arylamidase

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.

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
Keyword(s):  
Enzyme Activity ◽  
Enzyme System ◽  
Maximal Activity ◽  
Female Rats ◽  
Prostaglandin E ◽  
Degrading Enzyme ◽  
Oestrus Cycle ◽  
System L ◽  
Lh Release ◽  
Lh Rh

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.

SHORT-LOOP FEEDBACK MECHANISM OF LUTEINIZING HORMONE: LH STIMULATES HYPOTHALAMIC L-CYSTINE ARYLAMIDASE TO INACTIVATE LH-RH IN THE RAT HYPOTHALAMUS

1975 ◽  
Vol 78 (4) ◽  
pp. 649-663 ◽  
Author(s):  
Herbert Kuhl ◽  
Hans-Dieter Taubert
Keyword(s):  
Enzyme Activity ◽  
Feedback Mechanism ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Maximal Increase ◽  
Short Loop ◽  
Male And Female Rats ◽  
Loop Feedback ◽  
Lh Rh ◽  
Cystine Arylamidase

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.

THE INFLUENCE OF TIME, DOSE AND GONADAL STEROIDS ON LH-RH-INDUCED GONADOTROPHIN RELEASE IN RATS

1975 ◽  
Vol 78 (4) ◽  
pp. 695-704 ◽  
Author(s):  
Wolfgang Lotz
Keyword(s):  
Time Course ◽  
Time Lapse ◽  
Male Rats ◽  
Ovariectomized Rats ◽  
Response Curves ◽  
Intact Male ◽  
Maximal Increase ◽  
Serum Lh ◽  
Lh Rh ◽  
Lh Releasing Hormone

ABSTRACT Hypophyseal responses to LH-releasing hormone (LH-RH) were studied in ovariectomized rats, pre-treated once with 50 μg oestradiol-3-benzoate alone or in combination with 25 mg progesterone either 16, 24, 48 or 72 h before the administration of LH-RH. The highest serum gonadotrophin increase was detected in ovariectomized rats pre-treated with oestrogen 48 h before the LH-RH injection. The serum LH concentration change in intact male rats was markedly lower in terms of order of magnitude than in ovariectomized, oestradiol-3-benzoate, progesterone-treated rats ("O. Oe. P."-rats). These latter test animals showed the maximal increase of serum LH concentration, depending on the dose of LH-RH, after 10 to 25 min and that of FSH after 40 min. The dose-response curves for LH release in "O. Oe. P."-rats were linear for short (10 and 15 min) and sigmoid for longer time intervals (20, 30 and 40 min) between LH-RH injection and sacrifice. The possible reasons for the difference in both magnitude and time-lapse for maximal increase of serum LH and FSH concentration, the influence of steroid pre-treatment and the variation of the time-course of serum LH concentration, depending on the dose of LH-RH, are discussed.

STEROID PRIMING OF THE LUTEINIZING HORMONE RESPONSE TO LUTEINIZING HORMONE RELEASING HORMONE

1978 ◽  
Vol 77 (3) ◽  
pp. 293-299 ◽  
Author(s):  
L. V. BECK ◽  
M. BAY ◽  
A. F. SMITH ◽  
D. KING ◽  
R. LONG
Keyword(s):  
Luteinizing Hormone ◽  
Female Rats ◽  
Male Rats ◽  
Ovariectomized Rats ◽  
Normal Male ◽  
Initial Exposure ◽  
Luteinizing Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Pituitary Tissue ◽  
Lh Rh

Perifusion experiments were performed to study the stimulatory effects of luteinizing hormone releasing hormone (LH-RH) on the release of LH from anterior pituitary tissue. Exposure of pituitary tissue from normal male rats to LH-RH (5 ng/ml for 5 min) induced a small release of LH; in tissue from ovariectomized rats receiving no pretreatment, the release was more than three times greater and in tissue from gonadectomized male or female rats pretreated with oestradiol benzoate and progesterone, the release was six times greater than that observed in normal rats. Further exposure of pituitary tissue from gonadectomized steroid-pretreated male and female rats to LH-RH (5 ng/ml) induced an increase in the level of LH even greater than that seen after the initial exposure (priming action of LH-RH); in tissue from ovariectomized rats receiving no pretreatment, less LH was released than after the first exposure to LH-RH and in tissue from normal male rats the response was unchanged.

STIMULATION BY STEROIDS AND AGE-DEPENDENT CHANGES OF L-CYSTINE ARYLAMIDASE ACTIVITY IN THE HYPOTHALAMUS OF THE RAT

1974 ◽  
Vol 76 (1) ◽  
pp. 15-23 ◽  
Author(s):  
Herbert Kuhl ◽  
Christian Rosniatowski ◽  
Martin Bickel ◽  
Hans-Dieter Taubert
Keyword(s):  
Enzyme Activity ◽  
Sexual Maturation ◽  
Sexual Maturity ◽  
Male Rats ◽  
Age Dependent ◽  
Old Rats ◽  
Cystine Arylamidase ◽  
Ethinyl Oestradiol

ABSTRACT L-cystine arylamidase activity was found to be high in hypothalamic homogenates from 10 day old rats, and then to decrease significantly until sexual maturity was reached (P < 0.01). This enzyme activity could be stimulated by treating 10 to 35 day old male rats with 100 μg of testosterone. Contrary to this, L-cystine arylamidase activity could not be stimulated in female animals by the injection of 7 μg of ethinyl-oestradiol before Day 45 of life. These data are interpreted as meaning that the L-cystine arylamidase activity plays a rôle in the processes regulating sexual maturation.

Characteristics of Insulin-degrading Enzyme in Alzheimer's Disease: A Meta-Analysis

2018 ◽  
Vol 15 (7) ◽  
pp. 610-617 ◽  
Author(s):  
Huifeng Zhang ◽  
Dan Liu ◽  
Huanhuan Huang ◽  
Yujia Zhao ◽  
Hui Zhou
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Enzyme Activity ◽  
Protein Level ◽  
Senile Plaque ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Insulin Degrading Enzyme ◽  
Degrading Enzyme ◽  
Significant Difference

Background: β-amyloid (Aβ) accumulates abnormally to senile plaque which is the initiator of Alzheimer's disease (AD). As one of the Aβ-degrading enzymes, Insulin-degrading enzyme (IDE) remains controversial for its protein level and activity in Alzheimer's brain. Methods: The electronic databases PubMed, EMBASE, The Cochrane Library, OVID and Sinomed were systemically searched up to Sep. 20th, 2017. And the published case-control or cohort studies were retrieved to perform the meta-analysis. Results: Seven studies for IDE protein level (AD cases = 293; controls = 126), three for mRNA level (AD cases = 138; controls = 81), and three for enzyme activity (AD cases = 123; controls = 75) were pooling together. The IDE protein level was significantly lower in AD cases than in controls (SMD = - 0.47, 95% CI [-0.69, -0.24], p < 0.001), but IDE mRNA and enzyme activity had no significant difference (SMD = 0.02, 95% CI [-0.40, 0.43] and SMD = 0.06, 95% CI [-0.41, 0.53] respectively). Subgroup analyses found that IDE protein level was decreased in both cortex and hippocampus of AD cases (SMD = -0.43, 95% CI [-0.71, -0.16], p = 0.002 and SMD = -0.53, 95% CI [-0.91, -0.15], p = 0.006 respectively). However, IDE mRNA was higher in cortex of AD cases (SMD = 0.71, 95% CI [0.14, 1.29], p = 0.01), not in hippocampus (SMD = -0.26, 95% CI [-0.58, 0.06]). Conclusions: Our results indicate that AD patients may have lower IDE protease level. Further relevant studies are still needed to verify whether IDE is one of the factors affecting Aβ abnormal accumulation and throw new insights for AD detection or therapy.

Development of the renal response to blood volume expansion in normal and fast-growing rats

1976 ◽  
Vol 231 (3) ◽  
pp. 832-836
Author(s):  
HH Bengele ◽  
S Solomon
Keyword(s):  
Volume Expansion ◽  
Control Period ◽  
Male Rats ◽  
Regulatory Function ◽  
Chronological Age ◽  
Donor Blood ◽  
Fast Growing ◽  
Growing Rats ◽  
Blood Volume Expansion ◽  
Diuretic Response

Male rats from reduced (fast-growing) litters between 14 and 50 days of age were studied. Standard renal clearnce techniques were employed. After a 60-min control period, the animals were infused (2.3% body wt) with heparinized donor blood obtained from lillermates of the same age. Renal function was followed for an additional 60 min. The efficiency of the diuretic response, the percent infused volume excreted above control levels, and the sodium efficiency, the percent infused Na excreted, were calculated. Results indicate that both efficiencies develop in a discontinuous pattern and that they are comparable. This pattern of development, as well as the magnitude of the mature response, is comparable to that previously reported for rats from intact (normally growing) litters. The onset and attainment of the mature response is, however, shifted in time, such that reduced-litter animals achieve the mature response 10-15 days earlier than intact-litter rats. Results exclude chronological age or body weight alone as principal determinant of the mature response and suggest that some function of growth rate is responsible for the maturation of this regulatory function.

Serotonin-reinstatement of luteinizing hormone surges after loss of positive feedback in ovariectomized rats bearing subcutaneous capsules containing oestrogen

1983 ◽  
Vol 98 (1) ◽  
pp. 7-17 ◽  
Author(s):  
R. F. Walker
Keyword(s):  
Positive Feedback ◽  
Ovariectomized Rats ◽  
Facilitatory Effect ◽  
Serum Progesterone ◽  
Serotonin Content ◽  
Serum Lh ◽  
Serotonin Turnover ◽  
Lh Rh ◽  
Lh Releasing Hormone ◽  
Feedback Responses

In ovariectomized rats treated chronically with oestrogen there is a loss of positive feedback effects on LH secretion. This was not due to depletion of pituitary LH since injection of LH releasing hormone (LH-RH; 50 ng/100 g body wt) caused a significant (P < 0·01) rise in serum LH even after the loss of spontaneous LH surges. However, the magnitude of the increase in serum LH in response to LH-RH was greater (412 ± 41 μg/l) before than after (291 ± 29 μg/l) loss of the LH surges. Excessive blood sampling was also not responsible, since positive feedback responses declined comparably in rats bled daily or once every 3–4 days. Progesterone (0·5 mg s.c.), administered for 5 consecutive days, failed to restore LH surges indicating that deficiency of this steroid after ovariectomy does not cause positive feedback responses to disappear in rats exposed chronically to oestrogen. Moreover regular daily fluctuations in serum progesterone, probably of adrenal origin, occurred before as well as after daily LH surges were lost. Serotonin content and turnover were depressed (P < 0·05) when ovariectomized rats first received the subcutaneous capsules containing oestrogen. This change correlated temporally with the onset of daily LH surges and was eventually lost. After 30 days exposure to oestrogen, serotonin turnover increased (P < 0·01) and positive feedback responses were absent. Catecholamine levels and turnover did not show differential responses to oestrogen and were depressed after acute as well as chronic steroid treatment. p-Chlorophenylalanine (pCPA; 250 mg/kg)+ l-dihydroxyphenylalanine (l-DOPA; 200 mg/kg), which depress serotonin and enhance catecholamine synthesis respectively, failed to reinstate LH surges, but these were restored in 22% of the rats receiving l-DOPA alone. pCPA, followed 2 days later by 5-hydroxytryptophan (5-HTP) at 11.00 h, reinstated LH surges in 88% of rats, and a dose–response curve showed that as little as 4 mg 5-HTP/kg stimulated repetitive LH surges when given with pCPA according to this schedule. However, the administration of α-methyl-p-tyrosine + l-DOPA, an analogous treatment involving catecholamines, was only marginally effective (15%). These findings suggest that perturbations of monoamine metabolism occurring in ovariectomized rats exposed to oestrogen for several weeks contribute to loss of daily LH surges. Since pCPA + 5-HTP restored LH surges most effectively, then positive feedback may disappear as the facilitatory effect of serotonin is lost after chronic oestrogen administration.

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