scholarly journals Hypophysiotropic role of RFamide-related peptide-3 in the inhibition of LH secretion in female rats

2008 ◽  
Vol 199 (1) ◽  
pp. 105-112 ◽  
Author(s):  
Masahiro Murakami ◽  
Toshiya Matsuzaki ◽  
Takeshi Iwasa ◽  
Toshiyuki Yasui ◽  
Minoru Irahara ◽  
...  

Gonadotropin-inhibitory hormone (GnIH), a newly discovered hypothalamic RFamide peptide, inhibits reproductive activity by decreasing gonadotropin synthesis and release in birds. The gene of the mammalian RFamide-related peptides (RFRP) is orthologous to the GnIH gene. This Rfrp gene gives rise to the two biologically active peptides RFRP-1 (NPSF) and RFRP-3 (NPVF), and i.c.v. injections of RFRP-3 suppress LH secretion in several mammalian species. In this study, we show whether RFRP-3 affects LH secretion at the pituitary level and/or via the release of GnRH at the hypothalamus in mammals. To investigate the suppressive effects of RFRP-3 on the mean level of LH secretion and the frequency of pulsatile LH secretion in vivo, ovariectomized (OVX) mature rats were administered RFRP-3 using either i.c.v. or i.v. injections. Furthermore, the effect of RFRP-3 on LH secretion was also investigated using cultured female rat pituitary cells. With i.v. administrations, RFRP-3 significantly reduced plasma LH concentrations when compared with the physiological saline group. However, after i.c.v. RFRP-3 injections, neither the mean level of LH concentrations nor the frequency of the pulsatile LH secretion was affected. When using cultured pituitary cells, in the absence of GnRH, the suppressive effect of RFRP-3 on LH secretion was not clear, but when GnRH was present, RFRP-3 significantly suppressed LH secretion. These results suggest that RFRP-3 does not affect LH secretion via the release of GnRH, and that RFRP-3 directly acts upon the pituitary to suppress GnRH-stimulated LH secretion in female rats.

1999 ◽  
Vol 161 (3) ◽  
pp. 375-382 ◽  
Author(s):  
S Miyamoto ◽  
M Irahara ◽  
K Ushigoe ◽  
A Kuwahara ◽  
H Sugino ◽  
...  

We investigated the effect of activin A on secretion of LH, FSH, and prolactin (PRL) by female cultured rat pituitary cells at the single-cell level by means of the cell immunoblot assay. Anterior pituitary cells from 8-week-old female rats were preincubated with or without activin A for 24 h, after which they were monodispersed and immediately used for cell immunoblot assay. The percentages of LH-, FSH- and PRL-immunoreactive cell blots detected were 5.5, 5.3 and 43.1%, respectively, of all pituitary cells applied to the transfer membrane. The percentage of LH-secreting cells and mean LH secretion per cell did not change after treatment with activin. In contrast, activin significantly increased the percentage of FSH-secreting cells and mean FSH secretion per cell to 136.0 and 114. 5% respectively. In addition, activin significantly decreased the percentage of PRL-secreting cells and mean PRL secretion per cell to 52.2 and 72.0% respectively. These results suggest that (1) activin A has effects on female rat pituitary cells that increase not only the amount of FSH secretion per cell but also the number of FSH-secreting cells, and (2) activin A decreases both the amount of PRL secretion per cell and the number of PRL-secreting cells.


2009 ◽  
Vol 201 (3) ◽  
pp. 407-418 ◽  
Author(s):  
Shuisheng Li ◽  
Yong Zhang ◽  
Yun Liu ◽  
Xigui Huang ◽  
Weiren Huang ◽  
...  

To ascertain the neuroendocrine function of the kisspeptin/GPR54 system in non-mammalian species, full-length cDNAs encoding for Kiss1 and Kiss2 as well as their putative cognate receptors GPR54a and GPR54b, were isolated from goldfish (Carassius auratus). The deduced protein sequences between Kiss1 and Kiss2 in goldfish share very low similarity, but their putative mature peptides (kisspeptin-10) are relatively conserved. RT-PCR analysis demonstrated that the goldfish kiss1 gene (gfkiss1) is highly expressed in the optic tectum-thalamus, intestine, kidney, and testis, while the goldfish kiss2 gene (gfkiss2) is mainly detected in the hypothalamus, telencephalon, optic tectum thalamus, adipose tissue, kidney, heart, and gonads. The two receptor genes (gfgpr54a and gfgpr54b) are highly expressed in the brain regions including telencephalon, optic tectum thalamus, and hypothalamus. Both mature goldfish kisspeptin-10 peptides (gfKiss1–10 and gfKiss2–10) are biologically active as they could functionally interact with the two goldfish receptors expressed in cultured eukaryotic cells to trigger the downstream signaling pathways with different potencies. The actions of gfKiss1–10 and gfKiss2–10 on LH secretion were further investigated in vitro and in vivo. Intraperitoneal administration of gfKiss1–10 to sexually mature female goldfish could increase the serum LH levels. However, this peptide does not significantly influence LH release from goldfish pituitary cells in primary culture, indicating that the peptide does not exert its actions at the pituitary level. On the other hand, gfKiss2–10 appears to be a much less potent peptide as it exhibits no significant in vivo bioactivity and is also inactive on the primary pituitary cells.


2004 ◽  
pp. 397-403 ◽  
Author(s):  
M Tena-Sempere ◽  
ML Barreiro ◽  
E Aguilar ◽  
L Pinilla

OBJECTIVE: Raloxifene is a non-steroidal selective estrogen receptor modulator (SERM) that mimics estrogenic activity on bone density and blood lipid concentration without uterotropic actions. Previous data from our laboratory indicated that, as is the case for estrogen, neonatal administration of raloxifene disturbed normal differentiation of the hypothalamic circuitries governing the gonadotropic axis. In contrast, raloxifene did not act in the same way as estrogen does on the neuronal systems controlling sexual receptivity in the female rat. At present, however, the mechanisms for these organizing effects of raloxifene are not completely elucidated. DESIGN AND METHODS: To analyze this phenomenon, female rats were injected daily with raloxifene (50, 100, 250 or 500 microg/rat per day) between days 1 and 5 of age. On day 23, hypothalamic gonadotropin-releasing hormone (LHRH) mRNA expression was assessed, and pituitary and plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels were measured in basal and LHRH-stimulated conditions. In addition, LH and FSH responses to ovariectomy were evaluated in raloxifene-treated females. Finally, we monitored the ability of neonatal administration of a potent LHRH agonist ([d-Ala(6),d-Gly(10)]-LHRH ethylamide; 0.01 microg/kg per 12 h on days 1-5) to counteract the effects of raloxifene. RESULTS: Our analyses demonstrated that prepubertal rats (23-day-old females) treated neonatally with raloxifene showed decreased hypothalamic LHRH mRNA expression levels, reduced pituitary content of LH and FSH, reduced basal and LHRH-stimulated LH secretion in vivo and in vitro, and decreased response to ovariectomy. In addition, adult females treated neonatally with raloxifene showed anovulation and reduced serum LH levels; these effects were not prevented by the simultaneous administration of a LHRH agonist. CONCLUSION: In conclusion, our data demonstrate that neonatal administration of raloxifene can disrupt the programming of hypothalamic-pituitary-ovarian axis function. Reduced LH secretion, under basal and LHRH-stimulated conditions and after ovariectomy, is probably related to decreased LHRH expression, reduced pituitary LH content and/or decreased pituitary responsiveness to hypothalamic LHRH.


1985 ◽  
Vol 249 (3) ◽  
pp. E276-E280 ◽  
Author(s):  
W. S. Evans ◽  
R. J. Krieg ◽  
E. R. Limber ◽  
D. L. Kaiser ◽  
M. O. Thorner

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)


1980 ◽  
Vol 209 (1175) ◽  
pp. 299-315 ◽  

Aspects of the course of infection, growth and reproductive activity of Moniliformis were studied in adult male and female rats fed on iso -energetic purified diets containing various sugars. When rats were infected and fed on experimental diets containing either 3% glucose or 3% galactose for 5 weeks, very little growth of the worms and no signs of reproduction were observed. In contrast, Moniliformis grew well and showed many signs of normal reproduction when the rats were fed on diets containing either 3% fructose or 3% mannose. The ability of the worms to grow and reproduce was not lost by maintaining them first for 5 weeks in rats fed on diets containing 3% glucose and 3% galactose. When the diets of such rats were changed to ones containing 3% starch and 3% fructose, respectively, for a further 5 weeks, the worms grew and normal reproduction occurred. Similar experiments were carried out in which groups of infected rats were fed for 5 weeks on diets containing gradually increasing amounts of glucose (6-36%). It was not until the rats were fed on diets containing 24% glucose that the mean dry mass of the worms approached that of worms from rats fed on the diet con­taining 3% fructose; no host diet was found to be as effective a supporter of worm growth as 3% mannose. Under no circumstances, not even when the host’s diet contained 36%, was galactose found to be a suitable sugar for supporting the growth and reproduction of Moniliformis . Results consistent with those recorded for worms from rats fed on the diets containing monosaccharides were obtained when infected rats were fed for 5 weeks on diets containing 3% of various disaccharides. Considerable growth and reproduction of Moniliformis occurred when sucrose was included in the host’s diet, but not when lactose, maltose or trehalose was present. Several of these observations may be related to the fact that different sugars are absorbed at different rates from the intestinal tract. It is suggested that all of a given sugar, when present in the diet at a low concentration, may be removed rapidly from the anterior part of the small intestine with the result that none will be available to the parasites. Significant amounts, however, of those sugars that are absorbed more slowly may reach the region of the intestine in which the parasite normally lives.


1977 ◽  
Vol 74 (1) ◽  
pp. 99-109 ◽  
Author(s):  
D. DE ZIEGLER ◽  
M. WILKINSON ◽  
DANIELLE CASSARD ◽  
K. B. RUF

An investigation of pituitary sensitivity, assessed in terms of increments in plasma LH and FSH concentrations, to stimulation with one or two injections of gonadotrophin releasing hormone (GnRH) was carried out on 26-day-old immature female rats which had received one of the following priming treatments: 10 μg oestradiol benzoate (OB) as a single injection on day 23 or day 25, or on both days; 10 i.u. pregnant mare serum gonadotrophin (PMSG) on day 24; an electrochemical brain lesion placed in the mediobasal hypothalamus on day 23; control animals received either vehicle alone or a sham lesion. Pituitary sensitivity assessed at 10.00 h on day 26, after one or two injections of GnRH (100 ng/100 g body weight, s.c.), was enhanced to a similar degree in the three groups treated with OB in terms of LH (P < 0-01). The FSH response also increased after OB treatment but was not statistically significant. In contrast, 48 h after the injection of PMSG (i.e. when the rats were in a 'pro-oestrous-like' condition) pituitary sensitivity in terms of both LH and FSH dropped sharply (P < 0·001). In lesioned animals, pituitary sensitivity to one injection of GnRH was unchanged. A second GnRH injection administered after a 60 min interval induced a slightly larger LH response in control animals. In contrast, the ratio of the second response to the first increased in animals treated with PMSG, despite the state of overall decrease in sensitivity, being 4·5:1 in PMSG-treated rats versus 1·4:1 in controls. In a second set of experiments, we investigated the variation of pituitary sensitivity in conjunction with an experimentally induced gonadotrophin surge. In animals treated with OB on day 23 and with 1 mg progesterone at 12·00 h on day 26, pituitary sensitivity was increased at both 14.00 and 17.00 h as compared with that in the day 23 OB-treated group at 10.00 h. The PMSG-treated animals maintained their state of decreased responsiveness at 14.00 h, but exhibited increased pituitary sensitivity at the time of the gonadotrophin surge (17.00 h). These results show that OB increases pituitary sensitivity to GnRH in 26-day-old female rats and that the induction of a gonadotrophin surge further increases this sensitivity. In contrast, PMSG-treated rats displayed a state of decreased responsiveness 48 and 52 h, but not 55 h, after the injection. Pituitary sensitivity on the second day after PMSG treatment thus clearly differs from that observed during pro-oestrus in the adult cyclic female rat.


Endocrinology ◽  
2014 ◽  
Vol 156 (2) ◽  
pp. 600-612 ◽  
Author(s):  
Arturo E. Gonzalez-Iglesias ◽  
Patrick A. Fletcher ◽  
José A. Arias-Cristancho ◽  
Ruth Cristancho-Gordo ◽  
Cleyde V. Helena ◽  
...  

The peptide oxytocin (OT) is secreted by hypothalamic neurons and exerts numerous actions related to reproduction. OT stimulation of prolactin secretion in female rats is important during the estrous cycle, pregnancy, and lactation. Here we report that OT also stimulates transients of intracellular Ca2+ concentration in somatotrophs and gonadotrophs as well as the release of GH and LH in a dose-dependent manner with EC50 values that closely correspond to the ligand affinity of the OT receptor (OTR). Remarkably, the hormone-releasing effect of OT in these two cell types is 2 orders of magnitude more sensitive than that in lactotrophs. The specific OTR agonist [Thr4,Gly7]-oxytocin acutely stimulated the release of LH, GH, and prolactin from female rat pituitary cells in primary culture and increased intracellular Ca2+ concentration in gonadotrophs, somatotrophs, and lactotrophs. In these three cell types, the effects on hormone release and intracellular Ca2+ of both OT and [Thr4,Gly7]oxytocin were abolished by the specific OT receptor antagonist desGly-NH2-d(CH2)5[D-Tyr2,Thr4]OVT but not by the highly selective vasopressin V1a receptor antagonist, d(CH2)5[Tyr(Me)2,Dab5]AVP. Furthermore, 10 nM arginine vasopressin stimulated LH and GH release comparably with a dose of OT that was at least 10 times lower. Finally, the presence of the OTR-like immunoreactivity could be observed in all three cell types. Taken together, these results show that OT directly stimulates gonadotrophs, somatotrophs, and lactotrophs through OT receptors and suggest that OT signaling may serve to coordinate the release of different pituitary hormones during specific physiological conditions.


2020 ◽  
Vol 318 (2) ◽  
pp. R418-R427 ◽  
Author(s):  
Reham H. Soliman ◽  
Jermaine G. Johnston ◽  
Eman Y. Gohar ◽  
Crystal M. Taylor ◽  
David M. Pollock

Genes for the epithelial sodium channel (ENaC) subunits are expressed in a circadian manner, but whether this results in time-of-day differences in activity is not known. Recent data show that protein expression of ENaC subunits is higher in kidneys from female rats, yet females are more efficient in excreting an acute salt load. Thus, our in vivo study determined whether there is a time-of-day difference as well as a sex difference in the response to ENaC inhibition by benzamil. Our results showed that the natriuretic and diuretic responses to a single dose of benzamil were significantly greater in male compared with female rats whether given at the beginning of the inactive period [Zeitgeber time 0 (ZT0), 7 AM] or active period (ZT12, 7 PM). However, the response to benzamil was not significantly different between ZT0 and ZT12 dosing in either male or female rats. There was no difference in renal cortical α-ENaC protein abundance between ZT0 and ZT12 or males and females. Given previous reports of flow-induced stimulation of endothelin-1 (ET-1) production and sex differences in the renal endothelin system, we measured urinary ET-1 excretion to assess the effects of increased urine flow on intrarenal ET-1. ET-1 excretion was significantly increased following benzamil administration in both sexes, but this increase was significantly greater in females. These results support the hypothesis that ENaC activity is less prominent in maintaining Na+ balance in females independent of renal ET-1. Because ENaC subunit genes and protein expression vary by time of day and are greater in female rat kidneys, this suggests a clear disconnect between ENaC expression and channel activity.


2017 ◽  
Vol 233 (2) ◽  
pp. 159-174 ◽  
Author(s):  
Nilli Zmora ◽  
Ten-Tsao Wong ◽  
John Stubblefield ◽  
Berta Levavi-Sivan ◽  
Yonathan Zohar

Kisspeptin and neurokinin B (NKB) are neuropeptides co-expressed in the mammalian hypothalamus and coordinately control GnRH signaling. We have found that Nkb and kisspeptin neurons are distinct in the teleost, striped bass (STB) and capitalized on this phenomenon to study the mode of action of Nkb and its related neuropeptide-F (Nkf), both of which are encoded by the tac3 gene. In vitro brain slices and in vivo administration studies revealed that Nkb/f consistently downregulated kiss2, whereas antagonist (AntD) administration restored this effect. Overall, a minor effect was noted on gnrh1 expression, whereas Gnrh1 content in the pituitaries was reduced after Nkb/f treatment and increased with AntD. Concomitantly, immunostaining demonstrated that hypothalamic Nkb neurons border and densely innervate the largest kiss2 neuronal population in the hypothalamus, which also coexpresses Nkb receptor. No expression of Nkb receptor or Nkb neuronal projections was detected near/in Gnrh1 soma in the preoptic area. At the level of the pituitary, however, the picture was more complex: both Nkb/f and AntD upregulated lhb and fshb expression and Lh secretion in vivo. Together with the stimulatory effect of Nkb/f on Lh/Fsh secretion from pituitary cells, in vitro, this may indicate an additional independent action of Nkb/f within the pituitary, in which the hypothalamic pathway is more dominant. The current study demonstrates that Nkb/f utilizes multiple pathways to regulate reproduction in the STB and that in the brain, Nkb mainly acts as a negative modulator of kiss2 to regulate the release of Gnrh1.


1987 ◽  
Vol 116 (2) ◽  
pp. 165-171 ◽  
Author(s):  
Koji Nakagawa ◽  
Tatsuya Ishizuka ◽  
Takao Obara ◽  
Miyao Matsubara ◽  
Kazumasa Akikawa

Abstract. The mechanism of apparently discrepant actions of glucocorticoids (GC) on GH secretion, in vivo suppression and in vitro potentiation, was studied in rats. Dexamethasone (Dex), at the concentration of 50 nmol/l, Potentiated basal and GHRH-stimulated GH release from monolayer culture of normal rat pituitary cells in 48 h. On the other hand, in vivo administration of Dex, 165 μg daily for 3 days, consistently suppressed serum GH levels in female rats. In these rats, the hypothalamic content of immunoreactive (IR) SRIH was significantly increased, whereas that of IR-GHRH was significantly decreased in comparison with the untreated rats. Bioassayable GH-releasing activity was also lower in Dex-treated rats. These findings indicate that the suppressing effect of GC on GH release in vivo is, at least partially, due to the increase in hypothalamic SRIH release and probably also to the decrease in GHRH release, and these effects surpass the potentiating effect of GC on GH release at the pituitary level, resulting in a net inhibitory effect in vivo.


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