scholarly journals Kisspeptin Stimulates the Pulsatile Secretion of Luteinizing Hormone (LH) during Postpartum Anestrus in Ewes Undergoing Continuous and Restricted Suckling

Animals ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 2656
Author(s):  
José Manuel Hernández-Hernández ◽  
Graeme B. Martin ◽  
Carlos Miguel Becerril-Pérez ◽  
Arturo Pro-Martínez ◽  
César Cortez-Romero ◽  
...  
Keyword(s):  
Luteinizing Hormone ◽  
Jugular Vein ◽  
Pulse Frequency ◽  
Neural Pathways ◽  
Indwelling Catheter ◽  
Pulsatile Secretion ◽  
Intravenous Application ◽  
Access To Water ◽  
Ad Libitum ◽  
Lh Secretion

This study tested whether the intravenous application of kisspeptin can stimulate the pulsatile secretion of LH in suckling ewes during postpartum anestrus. Ten days after lambing, Pelibuey ewes were allocated among two groups: (1) continuous suckling (n = 8), where the lambs remained with their mothers; and (2) restricted suckling (n = 8), where the mothers suckled their lambs twice daily for 30 min. On Day 19 postpartum, the ewes were individually penned with ad libitum access to water and feed and given an indwelling catheter in each jugular vein. On Day 20, 4 mL of blood was sampled every 15 min from 08:00 to 20:00 h to determine LH pulse frequency. At 14:00 h, four ewes in each group received 120 μg of kisspeptin diluted in 3 mL of saline as a continuous infusion for 6 h; the remaining four ewes in each group received only saline. The interaction between kisspeptin and suckling type did not affect LH pulse frequency (p > 0.05). Before kisspeptin administration, pulse frequency was similar in all groups (1.50 ± 0.40 pulses per 6 h; p > 0.05). With the application of kisspeptin, pulse frequency increased to 3.50 ± 0.43 pulses per 6 h (p ≤ 0.014), so the concentration of LH (1.11 ± 0.14 ng mL−1) was greater in kisspeptin-treated ewes than in saline-treated ewes (0.724 ± 0.07 ng mL−1; p ≤ 0.040). The frequency of LH pulses was greater with restricted suckling than with continuous suckling (2.44 ± 0.29 versus 1.69 ± 0.29 pulses per 6 h; p ≤ 0.040). We conclude that intravenous application of kisspeptin increases the pulsatile secretion of LH in suckling ewes and that suckling might reduce kisspeptin neuronal activity, perhaps explaining the suppression of ovulation. Moreover, the effects of kisspeptin and suckling on pulsatile LH secretion appear to be independent, perhaps operating through different neural pathways.

Effects of oestradiol, progesterone and androstenedione on the pulsatile secretion of luteinizing hormone in ovariectomized ewes during spring and autumn

1983 ◽  
Vol 96 (2) ◽  
pp. 181-193 ◽  
Author(s):  
G. B. Martin ◽  
R. J. Scaramuzzi ◽  
J. D. Henstridge
Keyword(s):  
Luteinizing Hormone ◽  
Breeding Season ◽  
Negative Feedback ◽  
Combined Treatment ◽  
Pulse Frequency ◽  
The Other ◽  
Ovarian Steroids ◽  
Pulsatile Secretion ◽  
Lh Secretion

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.

scholarly journals Activation of Norepinephrine Neurons in the NTS (A2 population) is Sufficient to Suppress Pulsatile LH Secretion in Female Mice

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A531-A531
Author(s):  
Richard B McCosh ◽  
Michael J Kreisman ◽  
Katherine Tian ◽  
Steven A Thomas ◽  
Kellie M Breen
Keyword(s):  
Acute Stress ◽  
Cell Activity ◽  
Metabolic Stress ◽  
Pulse Frequency ◽  
Designer Drugs ◽  
Transduction Efficiency ◽  
Neural Pathways ◽  
Wild Type ◽  
Female Mice ◽  
Lh Secretion

Abstract The overarching goal of this work is to identify neural pathways underlying inhibition of pulsatile luteinizing hormone (LH) secretion during stress. Stress-induced suppression of LH secretion is mediated, at least in part, by suppression of arcuate kisspeptin (ARCKiss1) neurons. The mechanisms by which acute stress suppresses ARCKiss1 cell activity are largely unknown; however, several lines of evidence support the hypothesis that A2 neurons (norepinephrine [NE] neurons in the nucleus of the solitary tract [NTS] of the brainstem) are involved. First, A2 cells are activated during several reactive stress paradigms. Second, NE administered into the paraventricular nucleus, which is innervated by A2 neurons, suppressed pulsatile LH secretion. Finally, ablation of brainstem NE neurons restored estrous cyclicity following chronic glucoprivation (chronic metabolic stress model). The present study employed chemogenetics to test the hypothesis that A2 neurons are sufficient to suppress pulsatile LH secretion in ovariectomized female dopamine beta-hydroxylase (DBH) Cre positive and negative (wild type) mice. Mice received bilateral injections of either a Cre-dependent stimulatory Designer Receptor Exclusively Activated by Designer Drugs (DREADD) virus (AAV1-DIO-hM3Dq-mCherry) or a control virus (AAV1-DIO-mCherry) into the NTS. Mice were randomly assigned to receive either clozapine N-oxide (CNO, specific DREADD agonist; 1mg/kg, i.p.) or saline and blood samples were collected at 6-min intervals for 60 min before and 90 min after injection. Two weeks later, mice received the alternate treatment in a cross-over design (n= 5-10/grp). During the pre-injection period, all mice had clear LH pulses (mean: 6.0 ± 0.2 ng/mL, pulses/60 min: 3.4 ± 1.5). In DBH Cre- (wild type) mice with hM3D virus and DBH Cre+ with mCherry virus (both control groups), neither CNO nor saline altered mean LH or LH pulse frequency. However, DBH Cre+ mice with hM3D virus had a 54% reduction in mean LH (p < 0.05) and 59% reduction in pulse frequency (p < 0.05) following CNO; neither LH metric was altered in response to saline. To assess transduction efficiency, fixed neural tissue was collected. In tissue analyzed thus far, DBH Cre+ mice have mCherry labeling in ~70% of DBH-immunoreactive neurons in the NTS and >90% of mCherry neurons contained DBH immunoreactivity. Three DBH Cre+ mice with hM3D virus mice had no LH response to CNO and may represent missed viral injections, which will be determined when tissue is analyzed. These data demonstrate that activation of A2 neurons is sufficient to impair pulsatile LH secretion in female mice. Moreover, these data support the broad hypothesis that the A2 population of neurons is critical for modulating neuroendocrine function during stress and raises the possibility that A2 neurons directly or indirectly influence ARCKiss1 cell activity.

scholarly journals Neural Determinants of Pulsatile Luteinizing Hormone Secretion in Male Mice

Endocrinology ◽  
2020 ◽  
Vol 161 (2) ◽  
Author(s):  
Su Young Han ◽  
Isaiah Cheong ◽  
Tim McLennan ◽  
Allan E Herbison
Keyword(s):  
Luteinizing Hormone ◽  
High Frequency ◽  
Pulse Generator ◽  
Hormone Secretion ◽  
Pulse Frequency ◽  
Male Mice ◽  
Intact Male ◽  
Luteinizing Hormone Secretion ◽  
Pulse Profile ◽  
Lh Secretion

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.

Activation of a Classic Hunger Circuit Slows Luteinizing Hormone Pulsatility

2019 ◽  
Vol 110 (7-8) ◽  
pp. 671-687 ◽  
Author(s):  
Eulalia A. Coutinho ◽  
Melanie Prescott ◽  
Sabine Hessler ◽  
Christopher J. Marshall ◽  
Allan E. Herbison ◽  
...  
Keyword(s):  
Luteinizing Hormone ◽  
Ex Vivo ◽  
Polycystic Ovary ◽  
Brain Slices ◽  
Pulse Frequency ◽  
Pulse Generation ◽  
Electrophysiological Studies ◽  
The Impact ◽  
Lh Secretion

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.

Differential effects of electrolytic and chemical hypothalamic lesions on LH pulses in rats

1988 ◽  
Vol 255 (5) ◽  
pp. E583-E590 ◽  
Author(s):  
C. L. Sisk ◽  
A. A. Nunez ◽  
M. M. Thebert
Keyword(s):  
Luteinizing Hormone ◽  
Median Eminence ◽  
Arcuate Nucleus ◽  
Neuronal Cell ◽  
Pulse Frequency ◽  
Male Rats ◽  
Immunocytochemical Staining ◽  
Neuronal Cell Bodies ◽  
Electrolytic Lesions ◽  
Lh Secretion

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.

scholarly journals Estradiol Enables Chronic Corticosterone to Inhibit Pulsatile Luteinizing Hormone Secretion and Suppress Kiss1 Neuronal Activation in Female Mice

2019 ◽  
Vol 110 (6) ◽  
pp. 501-516 ◽  
Author(s):  
Michael J. Kreisman ◽  
Richard B. McCosh ◽  
Katherine Tian ◽  
Christopher I. Song ◽  
Kellie M. Breen
Keyword(s):  
Luteinizing Hormone ◽  
Hormone Secretion ◽  
Pulse Frequency ◽  
Dependent Manner ◽  
Neuronal Activation ◽  
Luteinizing Hormone Secretion ◽  
Female Mice ◽  
Enhanced Sensitivity ◽  
Ovarian Cyclicity ◽  
Lh Secretion

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.

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
Keyword(s):  
Luteinizing Hormone ◽  
Key Words ◽  
Dopaminergic System ◽  
Pulse Frequency ◽  
Steroid Dependent ◽  
Dependent Inhibition ◽  
And Control ◽  
Lh Secretion ◽  
Dopaminergic Pathways

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

Control of luteinizing hormone secretion in ewes by endogenous opioids and the dopaminergic system during short seasonal anoestrus: rôle of plane of nutrition

1997 ◽  
Vol 65 (2) ◽  
pp. 217-224 ◽  
Author(s):  
F. Forcada ◽  
J. M. Lozano ◽  
J. A. Abecia ◽  
L. Zarazaga
Keyword(s):  
Luteinizing Hormone ◽  
Receptor Antagonist ◽  
Dopaminergic System ◽  
Hormone Secretion ◽  
Pulse Frequency ◽  
Endogenous Opioids ◽  
Endogenous Opioid ◽  
Luteinizing Hormone Secretion ◽  
Lh Secretion

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.

Pituitary responsiveness to diurnal and nocturnal GnRH pulses in melatonin-treated ewe lambs

2000 ◽  
Vol 12 (2) ◽  
pp. 45 ◽  
Author(s):  
Sergio E. Recabarren ◽  
Alejandro Lobos ◽  
Emilio Cendoyya ◽  
Cristian Correa ◽  
Isolde Rudolph
Keyword(s):  
Luteinizing Hormone ◽  
Jugular Vein ◽  
Pulse Frequency ◽  
Ewe Lambs ◽  
Vein Catheter ◽  
High Responsiveness ◽  
Natural Photoperiod ◽  
Gonadotrophin Releasing Hormone ◽  
The Difference ◽  
And Control

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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