Leuprolide acetate affects intestinal motility in female rats before and after ovariectomy

1992 ◽  
Vol 262 (1) ◽  
pp. G185-G190
Author(s):  
R. Khanna ◽  
R. M. Browne ◽  
A. D. Heiner ◽  
M. H. Clench ◽  
J. R. Mathias

Leuprolide acetate, a gonadotropin-releasing hormone (GnRH) analogue, is currently being proposed to control debilitating symptoms in women with functional bowel disease. Whether leuprolide alters gastrointestinal motility as part of its actions is unknown. This study was designed to assess, using myoelectric techniques in an animal model, the effects of leuprolide on potential mechanisms of neuromuscular function of small intestine. Female rats with (n = 6) or without (n = 8) bilateral ovariectomy were used to study jejunal motility before and after leuprolide therapy. Throughout the study, daily leuprolide dosages of 0.02, 0.2, or 0.4 micrograms/kg were injected into intact rats and 0.02, 0.2, 0.4, 1.0, or 2.5 micrograms/kg into ovariectomized rats. Recordings were made while the rats were fasted and postprandial and before and after leuprolide administration. Under control conditions, migrating myoelectric complexes (MMCs) were found in intact female rats, whether fasted or postprandial. After ovariectomy, postprandial controls and those treated with low-dose leuprolide (0.02, 0.2, and 0.4 micrograms) had typical fed-state patterns and no MMCs, but at 1.0 and 2.5 micrograms the fed state was inhibited and cycling MMCs occurred at a frequency similar to that of fasted controls. Reproductive hormones thus have a significant effect on gastrointestinal motility.

1976 ◽  
Vol 71 (1) ◽  
pp. 31-36 ◽  
Author(s):  
JUDITH A. RAMALEY

SUMMARY The purpose of this study was to investigate adrenal function in rats during the development of persistent oestrus to determine whether a change in blood levels of corticosterone would precede or coincide with the onset of infertility. The syndrome of delayed persistent oestrus and anovulation was induced by administration of a low dose (10 μg) of testosterone propionate (TP) at 5 days of age. Control animals were handled without injection or received the vehicle (sesame oil) only. Half of each group was ovariectomized at weaning and received Silastic implants of either oestradiol benzoate (OB) or cholesterol, 3 mm tube length/100 g body weight. Intact rats given the low TP dose showed precocious vaginal opening (27·3 ± 2·1 days v. 37·6 ± 2·4 (s.e.m.) days in unhandled controls) and ovulated within 2 days. Persistent vaginal cornification developed in 22 out of 26 rats by 75 days of age. The TP-treated rats had higher corticosterone values than the controls and did not show a further increase after OB implantation. Cholesterol implantation depressed corticosterone levels in the TP-treated rats. The effects of the low TP dose were not dependent upon gonadal function since they persisted in ovariectomized rats. The results suggest that early exposure to androgen can modify the sensitivity of the adrenal system to oestrogen, and can also lead to persistently high values of corticosterone which are not depressed by ovariectomy. These changes precede the onset of persistent oestrus.


1987 ◽  
Vol 112 (1) ◽  
pp. 133-138 ◽  
Author(s):  
P. Södersten ◽  
P. Eneroth

ABSTRACT Ovariectomy and treatment with oestradiol benzoate (10 μg OB) on the day before behavioural oestrus eliminated the preovulatory surge of LH and reduced the level of sexual receptivity on the following day. Sexual behaviour, but not the LH surge, was restored by progesterone (0·5 mg) given 18 h later. Injection of OB on the day after behavioural oestrus induced a small release of LH and normal sexual behaviour on the following day. Ovariectomy on the day after behavioural oestrus reduced the stimulatory effect of OB on sexual behaviour and eliminated its weakly stimulatory effect on LH release. Sexual behaviour, but not the small LH surge, was restored in these animals by progesterone (0·5 mg) given 18 h later. Treatment of rats ovariectomized 2 days before the day of the LH surge with implants containing oestradiol or injections of oestradiol (1 μg) induced LH surges but the amplitudes of these LH surges were much smaller than those of the normal LH surge. Treatment of intact rats with OB increased serum progesterone levels 24 h later, an effect which was eliminated by ovariectomy. Injections of LH (20 μg) into intact rats on the day after behavioural oestrus also increased serum progesterone concentrations but failed to stimulate sexual behaviour. It is suggested that OB treatment of intact rats on the day after behavioural oestrus stimulates sexual behaviour by inducing a surge of LH secretion which activates ovarian secretion of progesterone. Thus, oestrogen and progesterone but not the LH surge are essential for sexual behaviour. Whereas oestradiol and progesterone restore normal sexual behaviour in ovariectomized rats, additional ovarian factors may be required for induction of normal LH surges. J. Endocr. (1987) 112, 133–138


1991 ◽  
Vol 125 (6) ◽  
pp. 581-589 ◽  
Author(s):  
Charla M. Blacker ◽  
Khalid M. Ataya ◽  
Ruth T. Savoy-Moore ◽  
Marappa G. Subramanian ◽  
Milton G. Mutchnick ◽  
...  

Abstract. To evaluate the effects of a gonadotropin-releasing hormone agonist on non-reproductive systems, we administered [D-Leu 6, Des-gly 10]-GnRH ethylamide (leuprolide; 5 μg/day) for 21 days to female Sprague-Dawley rats. In Experiment 1, continuous infusion (Alzet minipumps sc) was compared to injection. Increased thymus and body weights and decreased estradiol and uterine weights were noted for both administration methods. Spleen weight increased only in rats treated by continuous infusion. Ovary, kidney and liver weights did not change. Only leuprolide-injected rats had elevated LH with decreased corticosterone and ACTH levels, possibly related to the injection process. Glucose, insulin, progesterone, FSH and corticosterone/ACTH were not different. In Experiment 2, intact and ovariectomized rats were implanted with minipumps delivering leuprolide or 0.9% NaCl. Body and thymus weights increased, whereas uterine weight and estradiol declined in both leuprolide-treated and ovariectomized rats. No synergism between leuprolide and ovariectomy was noted. Thymosin α1, but not thymosin β4, increased in leuprolide-treated ovariectomized rats. Peripheral white blood cell count was elevated in leuprolide-treated intact rats and ovariectomized rats. In bone marrow, non-nucleated cell count declined in leuprolide-treated intact rats, contributing to the decreased total cell count in this group. Nucleated cell count was unaffected. Therefore, thymus weight gain was accompanied only in some cases by functional changes. Our results demonstrate that leuprolide affects non-reproductive systems, in a similar manner to ovariectomy. We suggest that such alterations may be due to the hypoestrogenic environment produced by leuprolide.


1979 ◽  
Vol 80 (1) ◽  
pp. 111-116 ◽  
Author(s):  
S. N. JUSTO ◽  
A. NEGRO-VILAR

A marked sexual difference in the rise of serum gonadotrophin concentrations after gonadectomy has been described in the rat. Gonadectomy in males induced a rapid rise in the concentrations of both LH and FSH within 8 to 12 h, whereas ovariectomy invoked a rapid increase in the concentration of FSH while the response by LH was delayed for several days. To determine whether these differences could be explained, at least in part, by the different steroid milieu at the time of gonadectomy, a series of experiments were performed to analyse the rise in both LH and FSH serum concentrations in control male and female rats and in male rats that had been pretreated with oestradiol-17β. Adult male rats received an s.c. implant of a silicone elastomer capsule filled with crystalline oestradiol-17 β. Controls received empty capsules. Twenty-four hours later, the oestradiol-implanted rats were castrated and control animals were sham-operated. Both LH and FSH levels remained within control levels after castration in the oestradiol-implanted rats, indicating that the oestradiol implant was preventing any rise of either gonadotrophin. On day 5 after implantation, the capsules were removed, sham-implanted animals were castrated and LH and FSH levels at 12, 24, 48 and 72 h were measured and compared with those of ovariectomized rats at similar intervals. The control male rats displayed the pattern of gonadotrophin increments normally found after castration, with both LH and FSH concentrations rising significantly by 12 h after castration and with further increments at later periods. Oestradiol-treated rats showed a female-like gonadotrophin pattern. FSH levels started to rise significantly at 24 h compared with values from intact rats and increased further at 48 and 72 h. During the first 48 h, FSH levels in both oestradiol-treated, castrated rats and female gonadectomized rats were significantly lower than in castrated animals. LH levels, on the other hand, remained low in both groups during the first 48 h, starting to rise significantly above control levels by 72 h. These results indicate that the different pattern of response to gonadectomy in rats of both sexes may be altered by changes in steroid environment and, therefore, may not be genetically predetermined.


Endocrinology ◽  
2003 ◽  
Vol 144 (10) ◽  
pp. 4253-4261 ◽  
Author(s):  
Emily C. Wasco ◽  
Elena Martinez ◽  
Katherine S. Grant ◽  
Emily A. St. Germain ◽  
Donald L. St. Germain ◽  
...  

The deiodinase types 2 and 3 (D2, D3), which convert T4 to active and inactive metabolites, respectively, are expressed in the rodent uterus and highly induced during pregnancy. To examine the factors regulating the expression of these enzymes in this tissue, we studied D2 and D3 activity in pregnant rats, in pseudopregnant rats before and after the induction of artificial decidualization, and in ovariectomized rats treated with 17β-estradiol (E2) and/or progesterone (P). Our results demonstrate that induction of D3 activity begins immediately after implantation and increases markedly over the next 72 h. A similar time course and magnitude of D3 induction is noted in the artificially decidualized uterus in pseudopregnant rats, whereas only minimal increases in activity are observed in the nondecidualized control uterine horns in the same animal. In contrast, D2 activity is not induced by a decidualization stimulus. In spontaneously cycling female rats, both D2 and D3 were observed to be 3- to 8-fold higher in proestrus, compared with diestrus. Furthermore, levels of D2 and D3 activity were greatly increased in ovariectomized rats given E2 and P in various combinations. D2 activity was stimulated primarily by E2, whereas E2 and P acted synergistically to increase D3 activity. These results demonstrate that E2 and P regulate thyroid hormone metabolism in the uterus, and that the implantation process is a potent stimulus for the induction of D3 activity in this organ. Such precise and profound changes in deiodinase expression are likely to play important physiological roles in fetal development and may influence uterine function.


1990 ◽  
Vol 123 (1) ◽  
pp. 61-66 ◽  
Author(s):  
Giovanni De Pergola ◽  
Agneta Holmäng ◽  
Jan Svedberg ◽  
Riccardo Giorgino ◽  
Per Björntorp

Abstract. The effects of testosterone treatment (2 mg every 14 days, for three months) on adipocyte lipolysis of intact (250-300 g body weight) and ovariectomized female rats were studied. Testosterone treatment of intact rats had no effect. Ovariectomy was followed by an increase in fat cell size and a decrease of lipolysis stimulated by isoproterenol, norepinephrine, epinephrine, forskolin, cAMP and isobutylmethylxantine. The number of βadrenergic receptors was reduced. There was, however, no change in the antilipolytic effects of UK 14,304 (alpha2-adrenergic agonist), nicotinic acid, N6-phenylisopropyladenosine or insulin. Testosterone treatment of ovariectomized rats restored the number of β-adrenoceptors and lipolysis stimulated by cAMP and isobutylmethylxantine, but not lipolysis stimulated by catecholamines and forskolin, suggesting a remaining defect in the catalytic unit of adenylate cyclase. These results indicate that ovariectomy is followed by a profound derangement of the lipolytic pathway at several levels, from β-adrenoceptors number to the triglyceride lipase activity. This is partially restored by treatment with testosterone, which, however, has no effect on intact female rats. This study emphasizes the importance of ovarian integrity for the lipolytic regulation and the inability of testosterone to replace ovarian function in this regard or to affect lipolysis in intact female rats.


2002 ◽  
Vol 283 (3) ◽  
pp. H1082-H1091 ◽  
Author(s):  
H. L. Xu ◽  
R. A. Santizo ◽  
V. L. Baughman ◽  
D. A. Pelligrino

It was previously shown that, despite the loss of nitric oxide (NO) dependence, ADP-induced pial arteriolar dilation was not attenuated in estrogen-depleted [i.e., ovariectomized (Ovx)] rats. Additional evidence suggested that the NO was replaced by an endothelium-dependent hyperpolarizing factor (EDHF)-like mechanism. To further characterize the nascent EDHF role in Ovx females, the current study was undertaken to test whether, in Ovx rats, ADP-induced pial arteriolar dilation retained its endothelial dependence and whether gap junctions are involved in that response. A closed cranial window and intravital microscopy system was used to monitor pial arteriolar diameter changes in anesthetized rats. The endothelial portion of the ADP-induced dilation was evaluated using light dye endothelial injury (L/D). The study was organized around three experimental approaches. First, the responses of pial arterioles to ADP before and after L/D exposure in intact and Ovx female rats were tested. L/D reduced the ADP response by 50–70% in both groups, thereby indicating that the endothelium dependence of ADP-induced vasodilation is not altered by chronic estrogen depletion. Second, the NO synthase inhibitor N ω-nitro-l-arginine (l-NNA) and the prostanoid synthesis inhibitor indomethacin (Indo) were coapplied. In intact females, l-NNA-Indo attenuated the response to ADP by 50%, with no further changes upon the addition of L/D. On the other hand, l-NNA-Indo did not affect ADP reactivity in Ovx rats, but subsequent L/D exposure reduced the ADP response by >50%. The NO-prostanoid-independent, but endothelium-dependent, nature of the response in Ovx females is a hallmark of EDHF participation. Third, gap junctional inhibition strategies were applied. A selective inhibitor of gap junctional function, Gap 27, did not affect ADP reactivity in intact females but reduced the the ADP response by 50% in Ovx females. A similar result was obtained following application of a connexin43 antisense oligonucleotide. These findings suggest that the nascent EDHF dependency of ADP-induced pial arteriolar dilation in Ovx females involves connexin43-related gap junctional communication.


2016 ◽  
Vol 21 (32) ◽  
pp. 8-12
Author(s):  
Абрамова ◽  
Marina Abramova ◽  
Алексеев ◽  
Vladimir Alekseev ◽  
Бойченко ◽  
...  

Electrical painful stimulation of pregnant female rats at the day before the birth leads to an increased activity of lysozyme in rat’s offspring in the womb. No differences were found between lysozyme activity in the rat’s blood, which were born from intact female rats and female rats with electrical painful stimulation.


Scientifica ◽  
2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Fatemeh Eshraghi-Jazi ◽  
Ardeshir Talebi ◽  
Fatemeh Sadat Mirsaeedi ◽  
Sarina Ahmadian ◽  
Fatemeh Moslemi ◽  
...  

Background. Gentamicin (GM) induced nephrotoxicity may be sex hormones related. The effects of sex hormones on GM induced nephrotoxicity in gonadectomized rats were investigated.Methods. Ovariectomized rats received 0.25, 0.5, or 1 mg/kg/week of estradiol (ES) alone or accompanied with 10 mg/kg/week of progesterone (Pro) for two weeks followed by GM (100 mg/kg/day) for 9 days. Castrated rats were also treated with 10, 50, or 100 mg/kg/week of testosterone (TS) for two weeks and then received GM. In addition, a single castrated group received 0.25 mg/kg/week of ES plus GM.Results. GM increased the serum levels of blood urea nitrogen (BUN) and creatinine (Cr) and kidney tissue damage score (KTDS) (P<0.05). TS had no effect on the serum levels of BUN and Cr and KTDS, while low dose of ES intensified these parameters in male (P<0.05). ES (0.5 mg/kg) without Pro ameliorated KTDS in female (P<0.05) while ES (1 mg/kg) with or without Pro exacerbated the BUN values and Cr values, KTDS, and body weight loss (P<0.05).Conclusion. ES (0.5 mg/kg) without Pro ameliorated kidney damage induced by GM in female while neither TS nor ES had beneficial effect on nephrotoxicity induced by GM in male, although ES aggravated it.


1991 ◽  
Vol 65 (05) ◽  
pp. 504-510 ◽  
Author(s):  
Raffaele De Caterina ◽  
Rosa Sicari ◽  
Walter Bernini ◽  
Guido Lazzerini ◽  
Giuliana Buti Strata ◽  
...  

SummaryTiclopidine (T) and aspirin (ASA) are two antiplatelet drugs both capable of prolonging bleeding time (BT), with a different mechanism of action. A synergism in BT prolongation has been reported and is currently considered an argument for not recommending their combination. However, a profound suppression of platelet function might be a desirable counterpart of a marked prolongation of BT, with a possible use in selected clinical situations. We therefore studied ex vivo platelet function (aggregation by ADP 0.5-1-2.5 μM; adrenaline 0.75-2.5 μM; collagen 1.5-150 μg/ml; arachidonic acid 1 mM; PAF 1 μM; adrenaline 0.17 μM + ADP 0.62 μM; serum thromboxane ([TX]B2 generation) and BT (Mielke) in 6 patients with stable coronary artery disease receiving such combination. Patients underwent sequential laboratory evaluations at baseline, after 7 days of T 250 mg b.i.d., before and after the intravenous administration of ASA 500 mg, respectively, and, finally, after a minimum of 7 days of sole ASA oral administration (50 mg/day). The experimental design, therefore, allowed a comparison of T and ASA effects (2nd and 4th evaluation), and an assessment of the combination effect (3rd evaluation). Platelet aggregation in response to all doses of ADP was depressed more by T than by ASA. Conversely, responses to adrenaline, and arachidonate were affected more by ASA than by T. For all other agents, differences were not significant. T + ASA combination was more effective (p <0.05) than either treatment alone in depressing responses to high-dose collagen (% over control, mean ± SEM: T: 95 ± 3; ASA: 96 ± 5; T + ASA: 89 ± 4). Serum TXB2 (basal, ng/ml: 380 ± 54) did not change with T (372 ± 36), dropped to <1 ng/ml on ASA injection and slightly re-increased to 9.1 ± 3.1 ng/ml on oral low-dose ASA. BT (basal 7.4 ± 0.6 min) was affected similarly by T (9.2 ± 0.8) or ASA (9.7 ± 0.9) alone, but increased to 15.0 ± 0.7 min on combination treatment (106% increase over control). Thus, the strong synergism in BT prolongation by ASA-T combination has a counterpart in the inhibition of platelet function in response to strong stimuli such as high-dose collagen, not otherwise affected significantly by single-drug treatment. This effect is a possible rationale for the clinical evaluation of T + ASA combination.


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