Involvement of cGMP in LHRH-stimulated gonadotropin release.

1978 ◽  
Vol 235 (6) ◽  
pp. E586 ◽  
Author(s):  
Z Naor ◽  
C P Fawcett ◽  
S M McCann
Keyword(s):  
Mechanism Of Action ◽  
Female Rats ◽  
Male Rats ◽  
Camp Content ◽  
Luteinizing Hormone Releasing Hormone ◽  
Gonadotropin Release ◽  
Male And Female Rats ◽  
The Relationship ◽  
Stimulation Of

Anterior pituitary content of cyclic AMP (cAMP) and cyclic GMP (cGMP) has been measured during stimulation of gonadotropin release by luteinizing-hormone-releasing hormone (LHRH) in vitro to gain more information concerning the relationship between the mechanism of action of LHRH and cyclic nucleotides. During the increased gonadotropin release obtained by incubation by hemipituitaries with LHRH (0.25--25 X 10(-9) M) for 180 min, the glands taken from both male and female rats exhibited increased cGMP content, whereas cAMP content rose only in those taken from male rats. The increase in cGMP content was observed after only 2 min in the presence of LHRH (5 X 10(-9) M) and prior to augmented gonadotropin release. The increase in cAMP content in the male glands was detectable only after 60 min of incubation. These results suggest that cGMP might be involved in the mechanism of action of LHRH.

Role of estrogens and age in flow-mediated outward remodeling of rat mesenteric resistance arteries

2014 ◽  
Vol 307 (4) ◽  
pp. H504-H514 ◽  
Author(s):  
K. Tarhouni ◽  
M. L. Freidja ◽  
A. L. Guihot ◽  
E. Vessieres ◽  
L. Grimaud ◽  
...  
Keyword(s):  
Blood Flow ◽  
Female Rats ◽  
Male Rats ◽  
Resistance Arteries ◽  
Cross Sectional ◽  
Male And Female ◽  
Male And Female Rats ◽  
Arterial Contractility

In resistance arteries, a chronic increase in blood flow induces hypertrophic outward remodeling. This flow-mediated remodeling (FMR) is absent in male rats aged 10 mo and more. As FMR depends on estrogens in 3-mo-old female rats, we hypothesized that it might be preserved in 12-mo-old female rats. Blood flow was increased in vivo in mesenteric resistance arteries after ligation of the side arteries in 3- and 12-mo-old male and female rats. After 2 wk, high-flow (HF) and normal-flow (NF) arteries were isolated for in vitro analysis. Arterial diameter and cross-sectional area increased in HF arteries compared with NF arteries in 3-mo-old male and female rats. In 12-mo-old rats, diameter increased only in female rats. Endothelial nitric oxide synthase expression and endothelium-mediated relaxation were higher in HF arteries than in NF arteries in all groups. ERK1/2 phosphorylation, NADPH oxidase subunit expression levels, and arterial contractility to KCl and to phenylephrine were greater in HF vessels than in NF vessels in 12-mo-old male rats only. Ovariectomy in 12-mo-old female rats induced a similar pattern with an increased contractility without diameter increase in HF arteries. Treatment of 12-mo-old male rats and ovariectomized female rats with hydralazine, the antioxidant tempol, or the angiotensin II type 1 receptor blocker candesartan restored HF remodeling and normalized arterial contractility in HF vessels. Thus, we found that FMR of resistance arteries remains efficient in 12-mo-old female rats compared with age-matched male rats. A balance between estrogens and vascular contractility might preserve FMR in mature female rats.

Different effects of (CIS+TRANS) 1,3-dichloropropene in renal cortical slices derived from male and female rats

1999 ◽  
Vol 18 (2) ◽  
pp. 106-110
Author(s):  
Livia Secondin ◽  
Stefano Maso ◽  
Andrea Trevisan
Keyword(s):  
Reduced Glutathione ◽  
Organic Anion ◽  
Female Rats ◽  
Male Rats ◽  
Aminooxyacetic Acid ◽  
Male And Female ◽  
Male And Female Rats ◽  
Cortical Slices

1 Nephrotoxic effects of 1,3-dichloropropene (cis and trans isomers mixture) was investigated in vitro by means of renal cortical slice model in male and female rats, including treatment with metabolism modifiers as an inducer of cytochrome P-450 1A class (β-naphtho-flavone), a reduced glutathione depleting (DL-buthio-nine-[S, R]-sulfoximine), an inhibitor of g-glutamyltransferase (AT-125) and inhibitor of cysteine conjugate β-lyase (aminooxiacetic acid).2 Dose-dependent decrease of p-aminohippurate uptake was observed in male renal cortical slices. Only the high doses (3.0 and 4.0×10-4M) caused a significant loss of organic anion uptake in females.3 β-Naphthoflavone and α-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (AT-125) partially, but significantly, reduced organic anion loss in males. In females, DL-buthionine-[S, R]-sulfoximine significantly increased in females but in males loss of organic anion accumulation caused by 1,3-dichloropropene. Aminooxyacetic acid did not ameliorate 1,3 D effects in vivo and in vitro in male rats. It appeared very toxic for female rats (all rats died) after in vivo injection.4 Sensitivity to nephrotoxicity induced by 1,3-dichlor-opropene in vitro was about double in male than female rats. Reduced glutathione conjugation appeared involved in nephrotoxicity induced in males but in females, probably by means of a chloropropylcysteinylglycine-conjugate formation; slight toxicity in females is likely related to oxidative metabolism.

EFFECTS OF TESTOSTERONE ON PITUITARY CORTICOTROPHIN AND ADRENAL STEROID SECRETION IN MALE AND FEMALE RATS

1963 ◽  
Vol 43 (4) ◽  
pp. 601-608 ◽  
Author(s):  
Julian I. Kitay
Keyword(s):  
Plasma Corticosterone ◽  
Female Rats ◽  
Male Rats ◽  
Intact Male ◽  
Male And Female ◽  
Adrenal Steroid ◽  
Adrenal Steroidogenesis ◽  
Male And Female Rats

ABSTRACT Administration of a depot testosterone preparation to male and female rats resulted in no change in body or pituitary weight in either sex. Pituitary corticotrophin content was unaltered in male animals but was reduced in females. Adrenal weights and adrenal RNA and DNA contents were decreased in both sexes. Plasma corticosterone concentrations were unaffected in males but were reduced in female rats after stress or corticotrophin injection. Hepatic reduction of ring A in vitro and biological half-life of corticosterone in vivo were unchanged in male animals but impaired in females. Testosterone administration to intact male rats significantly increased adrenal steroidogenesis measured in vitro. A significant decrease in steroid production was found in intact females but increased steroidogenesis was observed in adrenals from testosterone-treated oophorectomized animals. No effect was obtained following addition of testosterone directly in vitro. The data suggest that testosterone leads both to diminution of corticotrophin secretion and enhancement of adrenal steroid secretory capacity. In intact female rats, these effects are complicated by suppression of oestrogen secretion, the effects of which have been reported previously.

HYPOTHALAMIC LUTEINIZING HORMONE RELEASING FACTOR AND CORTICOTROPHIN RELEASING ACTIVITY IN RELATION TO PITUITARY AND PLASMA HORMONE LEVELS IN MALE AND FEMALE RATS

1977 ◽  
Vol 72 (2) ◽  
pp. 195-210 ◽  
Author(s):  
SHARON A. CHIAPPA ◽  
G. FINK
Keyword(s):  
Plasma Corticosterone ◽  
Female Rats ◽  
Male Rats ◽  
Male And Female ◽  
Male And Female Rats ◽  
Protein Binding Assay ◽  
Female Wistar Rats ◽  
Competitive Protein Binding Assay ◽  
Animal House

SUMMARY Hypothalamic corticotrophin releasing (CR) activity and LH-releasing factor (RF) content, and pituitary and plasma LH, FSH and ACTH were measured in adult male and female Wistar rats maintained under 14 h light per day. Hypothalamic LH-RF and pituitary and plasma hormones were estimated by radioimmunoassay while CR-activity was assessed by the amount of ACTH released from hemipituitaries in vitro. Two experiments were carried out on male animals. In the first, some of the animals were kept in a room, distant from the animal house, in which the lighting was reversed with respect to the external environment. In animals exposed to the reversed lighting régime, hypothalamic LH-RF content and pituitary gonadotrophin concentrations were significantly lower than the values in male rats kept in the animal house where they were in close proximity to female rats. In the second experiment, which was carried out on animals which had all been kept in the animal house, there were no significant differences between the LH-RF contents measured at 3–4 h intervals throughout the day. Pituitary LH and FSH contents, but not concentrations, were significantly increased at 12.00 h. There was little difference between the experiments in CR-activity, plasma ACTH concentrations and profiles of pituitary ACTH content and concentration. As expected there was a diurnal rhythm in plasma corticosterone concentrations (determined by competitive protein-binding assay) with the peak occurring between 15.00 and 18.00 h. The profiles of plasma and pituitary ACTH were similar to that of plasma corticosterone. Corticotrophin releasing activity dropped significantly between 12.00 and 16.00 h, but remained steady at the other times.

scholarly journals ALCOHOL ABOLISHES POST-STRESSOR AVERSION IN MALE RATS (POTENTIAL ROLE OF к-OPIOID RECEPTORS)

2018 ◽  
Vol 18 (1) ◽  
pp. 77-83
Author(s):  
V N Mukhin ◽  
A P Kozlov ◽  
I N Abdurasulova ◽  
K I Pavlov ◽  
V V Sizov ◽  
...  
Keyword(s):  
Opioid Receptors ◽  
Preference Test ◽  
Reward System ◽  
Female Rats ◽  
Male Rats ◽  
Final Conclusion ◽  
Alcohol Administration ◽  
Male And Female Rats ◽  
Stimulation Of

The probability of alcohol consumption by humans and experimental animals increases immediately after impact of stressors and remains at high level for some time. Neurobiological basis of this pattern is the effect of stress hormones on the mesolimbic system which is the core of the reward system in the brain that initiates learning processes. Literature data suggest that formation of aversive reactions depends on the system of dynorphin and к-opioid receptors which activates during the stress reaction. The purpose of this study was to investigate effect of alcohol administration on the post-stressor condition of the reward system and to clarify the role of к-opioid receptors in this. Experiment 1 aimed to investigation of post-stressor condition of the reward system in male and female rats and the influence of alcohol administration on it. Experiment 2 aimed to study whether alcohol affects the known from the literature aversive effect of che mical stimulation of к-opioid receptors as a model of post-stressor aversion. Methods. Appearance of preference or aversion to place where the rats were after action of the stressor was the indicator of the state of their reward syste m (place preference test). Result of the experiment 1. Condition of the reward syste m in the male rats was aversive 15 minutes after the end of the stressor action that caused avoidance of the context of environment in the future. Administration of alcohol after the end of the stressor action ceased this effect. Result of the experiment 2. Unlike the post-stressor aversion alcohol does not influence the aversion caused by stimulation of к-opioid receptors. Conclusion. Results of the study suggest that there is the aversive phase of the post-stressor state in the male rats that leads to formation of aversive associative reaction to the context of environment. Alcohol administration abolishes this phase. The involve ment of к- opioid receptors in this effect of alcohol is doubtful. But the final conclusion is possible only after direct experiment using antagonists.

Liver glycogenolysis during exercise in adrenodemedullated male and female rats

1986 ◽  
Vol 251 (6) ◽  
pp. R1151-R1155
Author(s):  
W. W. Winder ◽  
S. F. Loy ◽  
D. S. Burke ◽  
S. J. Hawkes
Keyword(s):  
Adrenergic Receptor ◽  
Mature Female ◽  
Female Rats ◽  
Male Rats ◽  
Plasma Epinephrine ◽  
Male And Female ◽  
Male And Female Rats ◽  
Liver Glycogenolysis ◽  
Stimulation Of

Previous studies have shown that adrenodemedullation has no effect on the rate of liver glycogenolysis during exercise in male rats. Mature female rats have been reported to have a higher hepatic beta-adrenergic receptor activity than do male rats of the same age. The present study was undertaken to determine the role of plasma epinephrine in stimulating liver glycogenolysis during exercise in female rats. Both male and female rats were adrenodemedullated or sham operated. Three weeks later rats were run for 60 min at 21 m/min up a 15% grade. The rate of liver glycogenolysis during exercise was not affected by adrenodemedullation in either female rats or male rats. Hepatic adenosine 3',5'-cyclic monophosphate increased to approximately the same extent in sham operated as in adrenodemedullated female rats during exercise. Adrenodemedullation caused a significant reduction in the amount of glycogen utilized by the soleus muscle and in the degree of hyperglycemia during exercise. We conclude that epinephrine is unessential for stimulation of liver glycogenolysis during exercise in either male or female rats.

EFFECT OF DEFICIENT DIETS ON CORTICOSTEROID SYNTHESIS BY RAT ADRENALS IN VITRO AND ITS RELATIONSHIP TO INFECTIONS WITH NIPPOSTRONGYLUS BRASILIENSIS

1969 ◽  
Vol 43 (3) ◽  
pp. 333-345 ◽  
Author(s):  
KAREN R. CLARKE
Keyword(s):  
Body Weight ◽  
Acquired Resistance ◽  
Female Rats ◽  
Male Rats ◽  
Adrenal Weight ◽  
Initial Contact ◽  
Nippostrongylus Brasiliensis ◽  
Male And Female Rats ◽  
Host Parasite

SUMMARY Rats were fed on a low protein (LP) and a glucose—filter paper (GFP) diet; they were then infected with 1000 larvae of the nematode worm Nippostrongylus brasiliensis (Travassos, 1914) and killed 5 or 10 days later. The adrenals of male and female rats on the GFP diet for 21 days showed atrophy and so did those of female rats on the LP diet for 42 or 56 days. The adrenals of male rats on the LP diet for 21 days were hypertrophic. Referred to body weight, the adrenal weights of male rats on both diets were higher than those of the controls, the weights of the adrenals of female rats on the deficient diets were lower. Adrenal weight and adrenal weight as a percentage of body weight were shown to bear no relationship to corticosteroid production in vitro, since the capacity for corticosteroid synthesis in vitro was increased in rats on the GFP diet only. Significantly more parasites were found in the intestine after 5, but not after 10 days on both deficient diets suggesting that the deficient diets increased the susceptibility of the rats on initial contact with the parasite and before the development of acquired resistance. Later more parasites were lost by the rats on the deficient diets than from controls. These findings were not related to changes in the rate of corticosteroid synthesis. The effects of stress, and the administration of cortisone or corticotrophin on host—parasite relationships is discussed in relation to the results of the present experiments. It is concluded that though these factors can increase susceptibility and lower acquired resistance, the effect on susceptibility can also be produced independently by severe dietary deficiency.

Characterization of the inhibitory roles of RFRP3, the mammalian ortholog of GnIH, in the control of gonadotropin secretion in the rat: in vivo and in vitro studies

2010 ◽  
Vol 299 (1) ◽  
pp. E39-E46 ◽  
Author(s):  
R. Pineda ◽  
D. Garcia-Galiano ◽  
M. A. Sanchez-Garrido ◽  
M. Romero ◽  
F. Ruiz-Pino ◽  
...  
Keyword(s):  
Inhibitory Effect ◽  
Female Rats ◽  
Male Rats ◽  
High Dose ◽  
Gonadotropin Secretion ◽  
Male And Female Rats ◽  
Sites Of Action ◽  
Lh Secretion

RF-amide related peptides (RFRP), as putative mammalian orthologs of the avian gonadotropin-inhibitory hormone (GnIH), have been proposed as key regulators of gonadotropin secretion in higher vertebrates. Yet considerable debate has arisen recently on their physiological relevance and potential mechanisms and sites of action. Present studies were undertaken to further characterize the effects of RFRP on LH and FSH secretion by a combination of in vivo and in vitro approaches in male and female rats. Initial screening via intracerebroventricular (icv) administration of different analogs of RFRP1 (RFRP1–12 and RFRP1–20) and RFRP3 (RFRP3–8 and RFRP3–17), as well as the related neuropeptide FF (NPFF8), to gonadectomized (GNX) female rats evidenced significant, albeit modest, inhibitory effects on LH secretion only for RFRP3–8 and RFRP3–17, which were detectable at the high dose rage (1 nmol for RFRP3–8, 5 nmol for RFRP3–17). This moderate inhibitory action was also documented after icv administration of RFRP3–8 to intact and GNX male rats. In addition, systemic (intravenous) administration of RFRP3–8 decreased the circulating levels of both gonadotropins in GNX male rats. Likewise, RFRP3–8 inhibited basal and GnRH-stimulated LH secretion by pituitaries from GNX males in vitro. This inhibitory effect was blocked by the antagonist of RFRP receptors, RF9. In summary, our results support a putative inhibitory role of RFRP3 as ortholog of GnIH in the regulation of gonadotropin secretion in mammals, which appears to involve direct pituitary actions as well as potential central (hypothalamic) effects.

Endogenous testosterone enhances growth hormone (GH)-releasing factor-induced GH secretion in vitro

1987 ◽  
Vol 113 (2) ◽  
pp. 249-253 ◽  
Author(s):  
L. Ohlsson ◽  
O. Isaksson ◽  
J.-O. Jansson
Keyword(s):  
Growth Hormone ◽  
Basal Medium ◽  
Dry Weight ◽  
Female Rats ◽  
Male Rats ◽  
Testosterone Replacement Therapy ◽  
Female Rat ◽  
Gh Secretion ◽  
Male And Female Rats

ABSTRACT The influence of endogenous gonadal steroids in male and female rats on basal and growth hormone-releasing factor (GRF)-stimulated GH secretion from perifused anterior pituitaries was studied. After 75 min of perifusion with basal medium, freshly dissected pituitaries were exposed to human GRF(1–44) (10 nmol/l) for 15 min. Neonatal (day 1–2) or prepubertal (day 25) gonadectomy of male rats suppressed baseline GH release (ng/min per mg dry weight) as well as GRF-stimulated GH release by 40–70%. This effect was slightly more pronounced in neonatally gonadectomized animals. In prepubertally gonadectomized male rats, the suppression of GH release was completely reversed by testosterone replacement therapy. In female rats, prepubertal gonadectomy did not affect GH secretion from perifused pituitaries. However, treatment of ovariectomized female rats with oestradiol reduced baseline and GRF-induced GH release to levels lower than those observed in sham-operated or vehicle-treated ovariectomized animals. The data suggest that testicular androgen secretion in adult male rats increases the pituitary GH release in response to GRF in vitro, whereas ovarian oestrogen secretion is of less importance for the GRF responsiveness of female rat pituitaries. J. Endocr. (1987) 113,249–253

Evolution of Design and Achievement of Inhibitors of the Luteinizing Hormone-Releasing Hormone as Inhibitors of Ovulation

1982 ◽  
Vol 37 (2) ◽  
pp. 246-259 ◽  
Author(s):  
Karl Folkers ◽  
John Humphries ◽  
Cyril Y. Bowers
Keyword(s):  
Luteinizing Hormone ◽  
Adult Male ◽  
Subcutaneous Tissue ◽  
Female Rats ◽  
Male Rats ◽  
Luteinizing Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Lh Rh

Abstract Detailed structure-activity studies on inhibitors of the luteinizing hormone releasing hormone (LH-RH) have been described. The most potent ovulation inhibitors have substitutions in positions 1, 2, 3, and 6. Currently four basic structural requirements for potent antiovulatory activity are: a D-aromatic amino acid, such as D-Trp or D-Phe, in position 6; a D-Phe residue in position 2; substitutions in positions 1 and 3. For inhibitors based on substitutions in positions 2, 3, and 6, the substitution of a Pro, N-Me-Leu or D-Trp residue in position 3 is equally acceptable, and gives analogues which inhibit ovulation at 750 ^g/rat. For inhibitors based on substitutions in positions 1, 2, 3, and 6, D-Trp appears necessary in position 3 in order for ovulation to be inhibited at 200 μ/rat. Many analogues based on the [residue1, D-Phe2, D-Trp3, D-Trp6]-LH-RH sequence are known which inhibit ovulation at 200 μ/rat. These include those analogues having D- <Glu, Ac-Pro, N-Ac-Hyp and N-Ac-Thr in position 1. The choice between L- or Dresidues in this position is structure dependent (Ac-L-Pro > Ac-D-Pro, D- <Glu >L- <Glu, etc.). In addition, a "protected" N-terminal residue having some polar character appears to be important. Substitution of the dipeptide residue, <Glu-Pro-, into position 1 has produced a new category of potent ovulation inhibitors based on linear peptides longer than decapeptides. Continued studies on other analogues in this later class could provide more potent inhibitors by (1) utilizing new binding sites on or in the vicinity of the LH-RH receptor(s); (2) altering transportation properties; (3) producing "pro-drugs". The substitution of N-Me-Leu into position 7 was not advantageous, presumably because of the presence of bulky D-aromatic amino acids in position 6. Nonapeptide ethylamide analogues also had very low antiovulatory potencies. The analogue [chlorambucil1, Leu2, Leu3, D-Ala6]-LH-RH acted as an agonist, but also inhibited in a modified assay in vitro. Comparative assays measuring the inhibition of LH-RH, and inhibition of ovulation have emphasized other factors of importance to inhibitor design. Although all ovulation inhibitors active at 750 or 200 /μg/rat strongly inhibited in vivo, at a ratio of analogue to LH-RH of 166:1, other analogues of comparable in vitro potency have displayed a range of antiovulatory activities. Similar discrepancies have been observed in the results of in vivo LH-RH inhibition assays. The most potent ovulation inhibitors always inhibited LH-RH at 333:1 in adult male chimpanzees, and at 100:1 in adult male rats. The dissociation of the results of the LH-RH and antiovulatory assays have been rationalized in two cases. The Cpc-analogues were active in inhibiting LH-RH in rats and in chimpanzees when given i.V., but were inactive in rats when given s.c. which is the mode of administration in the antiovulatory assay. The results for inhibition of LH-RH in vivo paralleled the results for inhibition of ovulation, and raised a question as to differences in absorption of peptides though the lipid layers of subcutaneous tissue. The reduced in vivo activities of the L-Trp3 analogues in both the LH-RH and antiovulatory assays suggest an increase in enzymatic inactivation for these compounds. [D-Phe2, Pro3, D-Phe6]-LH-RH can inhibit endogenous LH-RH in the Rhesus monkey and inhibit ovulation. Infusion of [D-Phe2, Pro3, D-Trp6]-LH-RH at 375 ^ug/day for 4 days from a s.c. implanted minipump completely inhibited ovulation in cycling female rats and decreased serum LH levels in castrated rats. In contrast with LH-RH or des-Gly10- [D-Ala6]-LH-RH ethylamide the Pro3 analogue did not block uterine implantation sites of mated rats, indicating a difference in the mechanism of contraception for LH-RH agonists and inhibitors

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