Regulation of LH secretion during seasonal anestrus by dopaminergic pathways in Rasa Aragonesa ewes treated or not with melatonin

2003 ◽  
Vol 83 (2) ◽  
pp. 311-313 ◽  
Author(s):  
F. Forcada ◽  
J. A. Abecia ◽  
O. Zúñiga

The involvement of the dopaminergic system in the steroid-dependent inhibition of luteinizing hormone (LH) secretion during anestrus in ovariectomized, estradiol-implanted adult Rasa Aragonesa ewes was investigated in both ewes treated with melatonin on 8 March (n = 10) and in control (n = 8) ewes. Melatonin implants did not significantly increase LH secretion. However, treatment with pimozide induced a significant increase (P < 0.05) in LH pulse frequency in both groups during early anestrus. We conclude that, in the absence of males, the dopaminergic system is clearly involved in the inhibition of LH secretion during anestrus in both melatonin-treated and control ewes. Key words: Sheep, melatonin, pimozide

1997 ◽  
Vol 65 (2) ◽  
pp. 217-224 ◽  
Author(s):  
F. Forcada ◽  
J. M. Lozano ◽  
J. A. Abecia ◽  
L. Zarazaga

AbstractThe role of endogenous opioids and the dopaminergic system on the inhibition of luteinizing hormone (LH) secretion during early and late anoestrus, together with its modulation by the plane of nutrition were investigated in ewes with a short anoestrous season. In early anoestrus (22 March; day 0), two groups of ovariectomized, oestradiol-treated adult Rasa Aragonesa ewes, maintained under natural photoperiod at 41°N, were given enough food to provide 1·4 × (high; H; no. = 6) or 0·5 × (low; L; no. = 6) energy requirements for maintenance. The effects of administration of the opiate receptor antagonist naloxone (1 mg/kg at four 1-h intervals) (day 15) and of the dopaminergic2 receptor antagonist pimozide (0·08 mg/kg) (day 21) on LH secretion were assessed. A second experiment was carried out in late anoestrus (21 June) using the same protocol. A significant increase in LH pulse frequency after naloxone treatment for both H and L groups was detected in late anoestrus. Number ofLH pulses after naloxone injections in early anoestrus also increased in H (P < 0·05) and L ewes (P = 0·08). The effect of pimozide injection on mean LH pulse frequency was greater in early than in late anoestrus, especially in ewes receiving a high plane of nutrition (P < 0·05 and P = 0·07 for H and L ewes, respectively in April and P = 0·07 for H ewes in July). A significant increase of LH pulse amplitude was also detected in early anoestrus in H ewes (P < 0·01). These results provide evidence that endogenous opioid mechanisms are involved in the inhibition ofLH pulsatile release both in early and late anoestrus in ewes with a short seasonal anoestrus. The ability of pimozide to increase LH pulse frequency in early anoestrus could be enhanced by a high plane of nutrition in the breed studied.


Endocrinology ◽  
2020 ◽  
Vol 161 (2) ◽  
Author(s):  
Su Young Han ◽  
Isaiah Cheong ◽  
Tim McLennan ◽  
Allan E Herbison

Abstract The gonadotrophin-releasing hormone (GnRH) pulse generator drives pulsatile luteinizing hormone (LH) secretion essential for fertility. However, the constraints within which the pulse generator operates to drive efficient LH pulsatility remain unclear. We used optogenetic activation of the arcuate nucleus kisspeptin neurons, recently identified as the GnRH pulse generator, to assess the efficiency of different pulse generator frequencies in driving pulsatile LH secretion in intact freely behaving male mice. Activating the pulse generator at 45-minute intervals generated LH pulses similar to those observed in intact male mice while 9-minute interval stimulation generated LH profiles indistinguishable from gonadectomized (GDX) male mice. However, more frequent activation of the pulse generator resulted in disordered LH secretion. Optogenetic experiments directly activating the distal projections of the GnRH neuron gave the exact same results, indicating the pituitary to be the locus of the high frequency decoding. To evaluate the state-dependent behavior of the pulse generator, the effects of high-frequency activation of the arcuate kisspeptin neurons were compared in GDX and intact mice. The same stimulus resulted in an overall inhibition of LH release in GDX mice but stimulation in intact males. These studies demonstrate that the GnRH pulse generator is the primary determinant of LH pulse profile and that a nonlinear relationship exists between pulse generator frequency and LH pulse frequency. This may underlie the ability of stimulatory inputs to the pulse generator to have opposite effects on LH secretion in intact and GDX animals.


2019 ◽  
Vol 110 (7-8) ◽  
pp. 671-687 ◽  
Author(s):  
Eulalia A. Coutinho ◽  
Melanie Prescott ◽  
Sabine Hessler ◽  
Christopher J. Marshall ◽  
Allan E. Herbison ◽  
...  

Introduction: The central regulation of fertility is carefully coordinated with energy homeostasis, and infertility is frequently the outcome of energy imbalance. Neurons in the hypothalamus expressing neuropeptide Y and agouti-related peptide (NPY/AgRP neurons) are strongly implicated in linking metabolic cues with fertility regulation. Objective: We aimed here to determine the impact of selectively activating NPY/AgRP neurons, critical regulators of metabolism, on the activity of luteinizing hormone (LH) pulse generation. Methods: We employed a suite of in vivo optogenetic and chemogenetic approaches with serial measurements of LH to determine the impact of selectively activating NPY/AgRP neurons on dynamic LH secretion. In addition, electrophysiological studies in ex vivo brain slices were employed to ascertain the functional impact of activating NPY/AgRP neurons on gonadotropin-releasing hormone (GnRH) neurons. Results: Selective activation of NPY/AgRP neurons significantly decreased post-castration LH secretion. This was observed in males and females, as well as in prenatally androgenized females that recapitulate the persistently elevated LH pulse frequency characteristic of polycystic ovary syndrome (PCOS). Reduced LH pulse frequency was also observed when optogenetic stimulation was restricted to NPY/AgRP fiber projections surrounding GnRH neuron cell bodies in the rostral preoptic area. However, electrophysiological studies in ex vivo brain slices indicated these effects were likely to be indirect. Conclusions: These data demonstrate the ability of NPY/AgRP neuronal signaling to modulate and, specifically, reduce GnRH/LH pulse generation. The findings suggest a mechanism by which increased activity of this hunger circuit, in response to negative energy balance, mediates impaired fertility in otherwise reproductively fit states, and highlight a potential mechanism to slow LH pulsatility in female infertility disorders, such as PCOS, that are associated with hyperactive LH secretion.


1994 ◽  
Vol 143 (1) ◽  
pp. 25-32 ◽  
Author(s):  
D J Tortonese ◽  
G A Lincoln

Abstract This study was conducted to investigate whether the photoperiodic regulation of the seasonal changes in pulsatile LH secretion in the ram involves changes in the activity of inhibitory hypothalamic dopaminergic (DA) pathways. To test this hypothesis, a series of experiments was carried out in Soay rams in which the effects of a DA-D2 receptor antagonist (sulpiride) or a DA-D2 receptor agonist (bromocriptine) on the pulsatile secretion of LH were determined under both long and short days. In each experiment blood samples were collected every 10 min for 8 h starting at the time of vehicle, sulpiride or bromocriptine injections to assess concentrations of LH. Sulpiride (0·59 mg/kg, s.c.) administered to rams under long days induced an immediate and sustained increase in the secretion of LH that lasted for approximately 4 h (P<0·05; ANOVA); this LH response reflected both a rise in mean concentrations (0·247 ± 0·03 vs.0·452 ± 0·1 μg/1) and an increase in the frequency of LH pulses (0·5±0·5 vs. 2·33±0·42 pulses/8 h; P<0·01). In contrast, under short days sulpiride had no effect. Bromocriptine (0·06 mg/kg, s.c.) administered to rams under long days, when LH concentrations were low, was without effect, but when given to rams under short days significantly (P<0·05) suppressed mean LH concentrations (0·627 ±0·08 vs. 0·320 ± 0·02 μg/l) and LH pulse frequency (4·86 ±0·46 vs. 2·43 ±0·37 pulses/8 h). In an additional experiment, pimozide (total dose: 0·16 mg/kg, i.m.), a DA antagonist less specific for DA-D2 receptors than sulpiride, was ineffective in modifying LH secretion in sexually inactive rams exposed to long days. These results are consistent with the hypothesis that an inhibitory dopaminergic system is involved in the regulation of pulsatile LH secretion in the ram. The induced changes in LH pulse frequency under long days (increased by sulpiride) and under short days (decreased by bromocriptine) indicate that, under both photoperiods, DA acts within the hypothalamus, via a specific DA-D2 receptor, to influence pulsatile GnRH secretion. A photoperiodic-induced activation of this inhibitory system may therefore represent the mechanism whereby long days suppress LH secretion and lead to the sexually inactive state characteristic of the non-breeding season. Journal of Endocrinology (1994) 143, 25–32


1983 ◽  
Vol 96 (2) ◽  
pp. 181-193 ◽  
Author(s):  
G. B. Martin ◽  
R. J. Scaramuzzi ◽  
J. D. Henstridge

The effects of oestradiol-17β, androstenedione, progesterone and time of the year on the pulsatile secretion of LH were tested in ovariectomized Merino ewes (n = 32). The steroids were administered by small subcutaneous implants, and the LH pulses were observed in samples taken at intervals of 15 min for 12 h in spring 1979, autumn 1980 and spring 1980, seasons corresponding to successive periods of anoestrus, breeding season and anoestrus. During spring, oestradiol alone was able to reduce the frequency of the LH pulses, while progesterone, either alone or in combination with oestradiol, had little effect. During autumn, on the other hand, neither oestradiol nor progesterone could significantly reduce the frequency of the pulses when administered independently, whereas the combined treatment was very effective. Androstenedione had no significant effect on pulse frequency at either time of the year, either alone or in any combination with oestradiol and progesterone. The basal levels of LH, over which the pulses are superimposed, were reduced by oestradiol alone in both seasons. Progesterone alone had no consistent effects, but interacted significantly with oestradiol and this combined treatment maintained low basal levels most effectively at all times. Androstenedione had no significant effect. The amplitude of the pulses increased throughout the course of the experiment. Within seasons, the amplitudes were significantly higher in the presence of oestradiol and progesterone, but were not significantly affected by androstenedione. It was concluded that certain of the ovarian steroids exert negative feedback on the tonic secretion of LH primarily by reducing the frequency of the pulses, and that the changes in LH secretion attributable to season and phases of the oestrous cycle can be accounted for entirely by the responses of the hypothalamus to oestradiol and progesterone. The role of the androstenedione secreted by the ovary in the ewe remains obscure.


1988 ◽  
Vol 255 (5) ◽  
pp. E583-E590 ◽  
Author(s):  
C. L. Sisk ◽  
A. A. Nunez ◽  
M. M. Thebert

Electrolytic lesions of the arcuate nucleus were made in anesthetized adult castrated male rats. Luteinizing hormone (LH) pulse frequency averaged 2.4 pulses/h in controls but declined to a mean of 0.5 pulses/h in rats with bilateral damage to the arcuate nucleus. Because these lesions also damaged the median eminence, we tested the possibility that this disruption of LH secretion was due to coincidental damage to fibers of passage projecting to median eminence. Axon-sparing chemical lesions of the arcuate nucleus were made by intracranial injections of N-methyl-DL-aspartate (NMA) in anesthetized adult castrated rats. Mean LH pulse frequency was 2.3 and 2.5 pulses/h in control and NMA-injected rats, respectively. NMA injections destroyed arcuate neuronal cell bodies and produced a proliferation of glial cells within the nucleus. There was no apparent difference in the immunocytochemical staining intensity and distribution of luteinizing hormone-releasing hormone (LHRH) fibers in median eminence in rats receiving NMA or sham injections. These results suggest that the disruptive effects of electrolytic lesions of the arcuate nucleus on pulsatile LH secretion are a result of coincidental damage to LHRH neuronal projections to the median eminence and that neuronal cell bodies within the arcuate nucleus are not necessary for normal pulsatile LH secretion in male rats.


2019 ◽  
Vol 110 (6) ◽  
pp. 501-516 ◽  
Author(s):  
Michael J. Kreisman ◽  
Richard B. McCosh ◽  
Katherine Tian ◽  
Christopher I. Song ◽  
Kellie M. Breen

Introduction: Two common responses to stress include elevated circulating glucocorticoids and impaired luteinizing hormone (LH) secretion. We have previously shown that a chronic stress level of corticosterone can impair ovarian cyclicity in intact mice by preventing follicular-phase endocrine events. Objective: This study is aimed at investigating if corticosterone can disrupt LH pulses and whether estradiol is necessary for this inhibition. Methods: Our approach was to measure LH pulses prior to and following the administration of chronic corticosterone or cholesterol in ovariectomized (OVX) mice treated with or without estradiol, as well as assess changes in arcuate kisspeptin (Kiss1) neuronal activation, as determined by co-expression with c-Fos. Results: In OVX mice, a chronic 48 h elevation in corticosterone did not alter the pulsatile pattern of LH. In contrast, corticosterone induced a robust suppression of pulsatile LH secretion in mice treated with estradiol. This suppression represented a decrease in pulse frequency without a change in amplitude. We show that the majority of arcuate Kiss1 neurons contain glucocorticoid receptor, revealing a potential site of corticosterone action. Although arcuate Kiss1 and Tac2 gene expression did not change in response to corticosterone, arcuate Kiss1 neuronal activation was significantly reduced by chronic corticosterone, but only in mice treated with estradiol. Conclusions: Collectively, these data demonstrate that chronic corticosterone inhibits LH pulse frequency and reduces Kiss1 neuronal activation in female mice, both in an estradiol-dependent manner. Our findings support the possibility that enhanced sensitivity to glucocorticoids, due to ovarian steroid milieu, may contribute to reproductive impairment associated with stress or pathophysiologic conditions of elevated glucocorticoids.


1991 ◽  
Vol 128 (3) ◽  
pp. 403-410 ◽  
Author(s):  
P. G. Knight ◽  
J. H. M. Wrathall ◽  
R. G. Glencross ◽  
B. J. McLeod

ABSTRACT It has been shown previously that treatment of seasonally anoestrous ewes with steroid-free bovine follicular fluid (FF), a crude inhibin-containing preparation, leads to a decrease in plasma FSH level which is accompanied by a marked increase in pulsatile LH secretion. Since FF contains several factors (e.g. activin, follistatin, unidentified components) other than inhibin, which might act to modify gonadotrophin secretion, it was of interest to establish whether these concurrent effects of FF on FSH and LH secretion persisted in ewes which had been actively immunized against a synthetic peptide replica of the α subunit of bovine inhibin. In June 1989 (anoestrous period) groups of inhibin-immune and control ewes (n = 5 per group) received 6-hourly s.c. injections of either bovine serum (2 ml) or one of two doses of FF (0·5 ml or 2 ml) for 3 days. Blood was withdrawn at 6-h intervals for 6 days beginning 24 h before the first injection. On the final day of treatment, additional blood samples were withdrawn at 15-min intervals for 8 h to monitor pulsatile LH secretion. Ewes were then challenged with exogenous gonadotrophin-releasing hormone (GnRH; 2 μg i.v. bolus) to assess pituitary responsiveness. In control ewes, FF promoted a dose-dependent suppression of basal (maximum suppression 65%; P < 0·01) and post-GnRH (maximum suppression 72%; P < 0·01) levels of FSH in plasma. This was accompanied by an increase (P < 0·01) in LH pulse frequency from 1·40±0·24 (s.e.m.) to 3·20±0·37 pulses/8 h. In contrast, FF did not affect secretion of either FSH or LH in inhibin-immunized ewes. However, mean plasma LH levels in immunized ewes were significantly lower (43%; P < 0·02) than in control ewes, irrespective of treatment. These findings indicate that in the anoestrous ewe the ability of FF to suppress plasma FSH is due entirely to its content of inhibin, that FF-induced enhancement of pulsatile LH secretion is mediated by inhibin, rather than some additional component of FF, and that immunoneutralization of endogenous inhibin can reduce LH secretion. Journal of Endocrinology (1991) 128, 403–410


1994 ◽  
Vol 74 (2) ◽  
pp. 273-279 ◽  
Author(s):  
C. Taylor ◽  
M. Manikkam ◽  
R. Rajamahendran

Twelve cyclic non-lactating cows were allocated at random to three treatment groups (IN, NP and 2N). Cows in the 1N group (n = 4) received an ear implant containing Norgestomet at pro-estrus (day 0 = day of Norgestomet-implant insertion). Cows in the NP group (n = 4) received a progesterone-releasing intravaginal device 3 d after a Norgestomet implant at pro-estrus, and cows in the 2N group (n = 4) received a second Norgestomet implant 3 d after the first implant at pro-estrus. Treatments were terminated on day 9. Ultrasonic examination of the ovaries was carried out before, during and after treatment to monitor follicular dynamics. Serial blood samples were collected every 15 min for 8 h from all cows on days 3 and 6 after initiation of treatments to characterize the luteinizing hormone (LH) profiles. The dominant follicle was maintained for 9 d in all IN cows, and upon implant removal all cows ovulated. In both NP and 2N cows, the dominant follicle regressed and a new cohort of small follicles appeared before the end of the treatment. The dominant follicle from this pool ovulated after implant removal in all NP cows. In the 2N group, only one cow ovulated after implant removal; the dominant follicles in the remainder became cystic and did not ovulate. Decreases in pulse frequency, amplitude and mean plasma LH were observed in the NP cows, compared with IN cows (P < 0.05), but no change in LH-pulse frequency was observed in the 2N cows. This study shows clearly that maintenance and regression of the dominant follicle are associated with changes in progesterone and LH environment. Key words: Progestin, dominant follicle, ultrasound, regression, luteinizing hormone, cattle


2000 ◽  
Vol 12 (2) ◽  
pp. 45 ◽  
Author(s):  
Sergio E. Recabarren ◽  
Alejandro Lobos ◽  
Emilio Cendoyya ◽  
Cristian Correa ◽  
Isolde Rudolph

It has been shown that oral administration of melatonin to Suffolk ewe lambs, from 10 weeks of age onwards, advances the onset of puberty compared with control lambs maintained under the same natural photope-riod. Luteinizing hormone (LH) pulse frequency at 20 and 26 weeks of age was unchanged by melatonin. However, LH pulse amplitudes greater than 1 ng mL –1 were consistently observed in melatonin-treated lambs, suggesting either a high responsiveness of the pituitary gland to endogenous gonadotrophin-releasing hormone (GnRH) pulses, or a large amount of GnRH released by each pulse. The purpose of the present study was to assess the pituitary responsiveness to six diurnal and six nocturnal exogenous pulses of GnRH (10 ng kg–1 bodyweight) in melatonin-treated ewe lambs (3 mg melatonin daily at 1600 hours, from 10 weeks of age; n = 5) and control lambs of the same age (n= 5), born in the spring and kept under natural photoperiod. Pulses of GnRH were given intravenously at 60-min intervals by means of an indwelling jugular catheter from 0900 to 1400 hours and from 2100 to 0200 hours to ewe lambs of 20 and 26 weeks of age. Blood samples were collected at 10-min intervals using a contralateral jugular vein catheter from 1 h before and up to 1 h after the last GnRH pulse. The difference (delta) between plasma LH concentrations at 0 min and the greatest concentration of LH after each GnRH pulse was calculated and compared in the same group. The total area under the GnRH response curve (AUC) was also calculated and compared within and between the groups. The AUC of melatonin-treated lambs (66.1 5.94 and 52.24 7.42 ng mL–1 /6 h, diurnal and nocturnal respectively) was greater than that of control lambs (39.42 4.29 and 32.82 3.6 ng mL –1 /6 h diurnal and nocturnal respectively; P<0.05) at 20 weeks of age. At 26 weeks of age, only the diurnal total AUC was greater in melatonin-treated lambs than in control lambs (60.17 7.98 and 29.8 5.02 ng mL –1 /6 h respectively; P<0.05). Delta LH concentrations in response to the first diurnal pulse of GnRH were greater than those in response to the fifth diurnal GnRH pulse (P<0.05) in melatonin-treated lambs of 20 weeks of age. Also, the delta LH concentrations in response to the first three diurnal GnRH pulses were greater than to the last three nocturnal pulses of GnRH (P<0.05). Delta LH concentrations were greater in response to the second diurnal pulse of GnRH than to the last three diurnal GnRH pulses, and greater than the responses to the first and the last four nocturnal GnRH pulses (P<0.05), at 26 weeks of age in melatonin-treated lambs. The response to nocturnal pulses of GnRH was similar. In control lambs, the responses to diurnal and nocturnal GnRH pulses were similar at 20 and 26 weeks of age. These results suggest that melatonin enhances the pituitary responsiveness to GnRH pulses in ewe lambs. Extra key words: luteinizing hormone, sheep.


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