scholarly journals Changes in RFamide-Related Peptide-1 (RFRP-1)-Immunoreactivity During Postnatal Development and the Estrous Cycle

Endocrinology ◽  
2014 ◽  
Vol 155 (11) ◽  
pp. 4402-4410 ◽  
Author(s):  
Sara R. Jørgensen ◽  
Mille D. Andersen ◽  
Agnete Overgaard ◽  
Jens D. Mikkelsen
Keyword(s):  
Postnatal Development ◽  
Estrous Cycle ◽  
Third Ventricle ◽  
Female Rats ◽  
Male Rats ◽  
Relative Distribution ◽  
Gonadotropin Secretion ◽  
Related Peptide

Abstract GnRH is a key player in the hypothalamic control of gonadotropin secretion from the anterior pituitary gland. It has been shown that the mammalian counterpart of the avian gonadotropin inhibitory hormone named RFamide-related peptide (RFRP) is expressed in hypothalamic neurons that innervate and inhibit GnRH neurons. The RFRP precursor is processed into 2 mature peptides, RFRP-1 and RFRP-3. These are characterized by a conserved C-terminal motif RF-NH2 but display highly different N termini. Even though the 2 peptides are equally potent in vitro, little is known about their relative distribution and their distinct roles in vivo. In this study, we raised an antiserum selective for RFRP-1 and defined the distribution of RFRP-1-immunoreactive (ir) neurons in the rat brain. Next, we analyzed the level of RFRP-1-ir during postnatal development in males and females and investigated changes in RFRP-1-ir during the estrous cycle. RFRP-1-ir neurons were distributed along the third ventricle from the caudal part of the medial anterior hypothalamus throughout the medial tuberal hypothalamus and were localized in, but mostly in between, the dorsomedial hypothalamic, ventromedial hypothalamic, and arcuate nuclei. The number of RFRP-1-ir neurons and the density of cellular immunoreactivity were unchanged from juvenile to adulthood in male rats during the postnatal development. However, both parameters were significantly increased in female rats from peripuberty to adulthood, demonstrating prominent gender difference in the developmental control of RFRP-1 expression. The percentage of c-Fos-positive RFRP-1-ir neurons was significantly higher in diestrus as compared with proestrus and estrus. In conclusion, we found that adult females, as compared with males, have significantly more RFRP-1-ir per cell, and these cells are regulated during the estrous cycle.

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.

Effects of in vivo gonadal hormone environment on in vitro hGRF-40-stimulated GH release

1985 ◽  
Vol 249 (3) ◽  
pp. E276-E280 ◽  
Author(s):  
W. S. Evans ◽  
R. J. Krieg ◽  
E. R. Limber ◽  
D. L. Kaiser ◽  
M. O. Thorner
Keyword(s):  
Female Rats ◽  
Male Rats ◽  
Gonadal Hormone ◽  
Base Line ◽  
Pituitary Cells ◽  
Intact Male ◽  
Castrate Male ◽  
Basal Release

The effects of gender and the gonadal hormone environment on basal and stimulated growth hormone (GH) release by dispersed and continuously perifused rat anterior pituitary cells were examined. Cells from intact male and diestrus day 2 female rats and from castrate male rats either untreated or treated with testosterone (T) or 17 beta-estradiol (E2) were used. Basal GH release (ng/min per 10(7) cells; mean +/- SE) by cells from diestrus day 2 female rats was less than by cells from castrate rats treated with T (4.3 +/- 0.6 vs. 11.4 +/- 2.7, respectively; P less than 0.025). No other differences in basal release were detected. Concentration-response relationships were documented between human GH-releasing factor 40 (hGRF-40; 0.03-100 nM given as 2.5-min pulses every 27.5 min) and GH release. Mean (+/- SE) overall GH release (ng/min per 10(7) cells) above base line was greater by cells from intact male rats (496 +/- 92) than by cells from castrate (203 +/- 37.3; P less than 0.0001), castrate and T-treated (348 +/- 52.8; P = 0.008), or castrate and E2-treated (58.1 +/- 6.8; P less than 0.001) male rats or by diestrus day 2 rats (68.6 +/- 9.5; P = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

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.

scholarly journals Agouti Related Peptide (Agrp) Stimulates the Hypothalamo Pituitary Gonadal Axis in Vivo & in Vitro in Male Rats

Endocrinology ◽  
1999 ◽  
Vol 140 (11) ◽  
pp. 5459-5462 ◽  
Author(s):  
S. A. Stanley ◽  
C. J. Small ◽  
M. S. Kim ◽  
M. M. Heath ◽  
L. J. Seal ◽  
...  
Keyword(s):  
Male Rats ◽  
Related Peptide

Effects of Ghrelin upon Gonadotropin-Releasing Hormone and Gonadotropin Secretion in Adult Female Rats: In vivo and in vitro Studies

2005 ◽  
Vol 82 (5-6) ◽  
pp. 245-255 ◽  
Author(s):  
Rafael Fernández-Fernández ◽  
Manuel Tena-Sempere ◽  
Víctor M. Navarro ◽  
María L. Barreiro ◽  
Juan M. Castellano ◽  
...  
Keyword(s):  
Adult Female ◽  
Gonadotropin Releasing Hormone ◽  
In Vitro Studies ◽  
Female Rats ◽  
Gonadotropin Secretion ◽  
Releasing Hormone

scholarly journals Direct stimulatory effect of ghrelin on pituitary release of LH through a nitric oxide-dependent mechanism that is modulated by estrogen

Reproduction ◽  
2007 ◽  
Vol 133 (6) ◽  
pp. 1223-1232 ◽  
Author(s):  
Rafael Fernández-Fernández ◽  
Manuel Tena-Sempere ◽  
Juan Roa ◽  
Juan Manuel Castellano ◽  
Víctor M Navarro ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Reproductive Function ◽  
Female Rats ◽  
Experimental Conditions ◽  
Gonadotropin Secretion ◽  
Minimal Effective Dose ◽  
Gh Secretion ◽  
Lh Secretion

Ghrelin, a gut peptide with key actions on food intake and GH secretion, has been recently recognized as potential regulator of reproductive function. Thus, in adult female rats, ghrelin has been proven to modulate GnRH/LH secretion, with predominant inhibitory effectsin vivo. We analyze herein potential direct pituitary effects of ghrelin on basal and GnRH-stimulated gonadotropin secretion in prepubertal female rats, and its interplay with ovarian inputs, nitric oxide (NO), and hypothalamic differentiation. In the experimental setting, pituitaries from intact and ovariectomized prepubertal female rats were challenged with ghrelinin vitroand LH secretion was monitored. Our results demonstrate that 1) ghrelin consistently stimulatedin vitropituitary LH secretion under different experimental conditions; 2) the sensitivity to ghrelin, expressed either as the minimal effective dose or the amplitude of the LH response, was modulated by ovarian inputs; 3) the blockade of estrogen action significantly augmented the stimulatory effect of ghrelin; 4) the stimulatory effect of ghrelin on LH secretion required proper NO synthesis; and 5) the ability of ghrelin to elicit LH secretionin vitrowas preserved after alteration (masculinization) of brain sexual differentiation. Overall, our present data reinforce the concept that ghrelin participates in the control of LH secretion, with potential stimulatory actions at the pituitary level that require the presence of NO and are modulated by ovarian signals.

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.

scholarly journals Some Biochemical and Histological Effects of 2-Chloroethanol in Rats

1992 ◽  
Vol 1 (3) ◽  
pp. 37-56 ◽  
Author(s):  
Leonard Friedman ◽  
John Scalera ◽  
James E. Keys ◽  
Edmund L. Peters ◽  
Dennis W. Gaines ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Rna Synthesis ◽  
Liver Lipid ◽  
Intraperitoneal Administration ◽  
Female Rats ◽  
Male Rats ◽  
Liver Protein ◽  
Adult Rats

The effects of 2-chioroethanol (2-CE) on rat tissue following in vitro and in vivo exposure were studied. At concentrations as low as 2.5 mg/ml, protein synthesis in liver slices was inhibited; at concentrations of 25 mg/ml and above, RNA synthesis and respiration were also impaired. Single oral doses of 2-CE to young adult rats at levels of 15-40 mg/kg body weight depressed liver nonprotein sulfhydryl (GSH) concentration and liver protein but not RNA synthesis. Liver lipid was increased by 7 hr after a single oral dose of 30 mg/kg. The time courses and dose-response relationship for GSH depletion and restoration and for protein synthesis inhibition and recovery were similar. The livers of female rats were more sensitive than the livers of male rats to the effects of 2-CE. Protein synthesis was also depressed in kidneys of 2-CE-treated male rats but at higher doses than those needed for this effect to occur in livers of the same animals. Liver polysome disaggregation also occurred after oral 2-CE doses of 20 mg/kg and greater. The effects of 2-CE on ribosome profiles and protein synthesis were at least partially reversed by concurrent intraperitoneal administration of cysteine. The possible relationship of these findings to a role of GSH in protein synthesis is discussed.

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.

scholarly journals Characterization of the Potent Gonadotropin-Releasing Activity of RF9, a Selective Antagonist of RF-Amide-Related Peptides and Neuropeptide FF Receptors: Physiological and Pharmacological Implications

Endocrinology ◽  
2010 ◽  
Vol 151 (4) ◽  
pp. 1902-1913 ◽  
Author(s):  
R. Pineda ◽  
D. Garcia-Galiano ◽  
M. A. Sanchez-Garrido ◽  
M. Romero ◽  
F. Ruiz-Pino ◽  
...  
Keyword(s):  
Female Rats ◽  
Central Administration ◽  
Gonadotropin Secretion ◽  
Male And Female ◽  
Selective Antagonist ◽  
Male And Female Rats ◽  
Neuropeptide Ff ◽  
Gonadotropin Inhibitory Hormone

Identification of RF-amide-related peptides (RFRP), as putative mammalian orthologs of the avian gonadotropin-inhibitory hormone, has drawn considerable interest on its potential effects and mechanisms of action in the control of gonadotropin secretion in higher vertebrates. Yet, these analyses have so far relied mostly on indirect approaches, while direct assessment of their physiological roles has been hampered by the lack of suitable antagonists. RF9 was recently reported as a selective and potent antagonist of the receptors for RFRP (RFRPR) and the related neuropeptides, neuropeptide FF (NPFF) and neuropeptide AF (NPFF receptor). We show here that RF9 possesses very strong gonadotropin-releasing activities in vivo. Central administration of RF9 evoked a dose-dependent increase of LH and FSH levels in adult male and female rats. Similarly, male and female mice responded to intracerebroventricular injection of RF9 with robust LH secretory bursts. In rats, administration of RF9 further augmented the gonadotropin-releasing effects of kisspeptin, and its stimulatory effects were detected despite the prevailing suppression of gonadotropin secretion by testosterone or estradiol. In fact, blockade of estrogen receptor-α partially attenuated gonadotropin responses to RF9. Finally, systemic administration of RF9 modestly stimulated LH secretion in vivo, although no direct effects in terms of gonadotropin secretion were detected at the pituitary in vitro. Altogether, these data are the first to disclose the potent gonadotropin-releasing activity of RF9, a selective antagonist of RFRP (and NPFF) receptors. Our findings support a putative role of the RFRP/gonadotropin-inhibitory hormone system in the central control of gonadotropin secretion in mammals and have interesting implications concerning the potential therapeutic indications and pharmacological effects of RF9.

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