Plasma β-endorphin and LH during prolonged hypoglycaemia in ewes

Normal reproductive function in female animals can be drastically impaired by a variety of stressful stimuli. For example, undernutrition and hypoglycaemia in sheep have been shown to suppress pulsatile LH secretion and to reduce the number of ewes showing pre-ovulatory LH peaks (Crump and Rodway 1986, Clarke et al. 1990). Similar stresses are also known to cause release of the opioid peptide β-endorphin into the circulation. Opioids are well-known to have a central inhibitory effect on LH release, although whether the elevated plasma concentrations of these peptides have any effect on LH secretion is unclear. The present study investigated the affect of insulin-induced hypoglycaemia on plasma concentrations of β-endorphin and LH.

Unsaturated Fatty Acids Stimulate LH Secretion via Novel PKCε and -θ in Gonadotrope Cells and Inhibit GnRH-Induced LH Release

Endocrinology ◽

10.1210/en.2011-1167 ◽

2011 ◽

Vol 152 (10) ◽

pp. 3905-3916 ◽

Cited By ~ 28

Author(s):

Ghislaine Garrel ◽

Violaine Simon ◽

Chantal Denoyelle ◽

Céline Cruciani-Guglielmacci ◽

Stéphanie Migrenne ◽

...

Keyword(s):

Fatty Acids ◽

Cell Cultures ◽

Unsaturated Fatty Acids ◽

Reproductive Function ◽

Peroxisome Proliferator ◽

Mrna Levels ◽

Dependent Manner ◽

Lh Release ◽

The activity of pituitary gonadotrope cells, crucial for reproductive function, is regulated by numerous factors including signals related to nutritional status. In this work, we demonstrated, for the first time, that in vivo central exposure of rats to lipids intracarotid infusion of a heparinized triglyceride emulsion selectively increases the expression of pituitary LH subunit genes without any alteration of pituitary GnRH receptor and hypothalamic GnRH or Kiss-1 transcript levels. Furthermore, we showed that unsaturated fatty acids (UFA), oleate and linoleate, increase LH release in a dose-dependent manner as well as LHβ mRNA levels in both immortalized LβT2 gonadotrope cell line and rat primary cell cultures. In contrast, the saturated palmitate was ineffective. ACTH or TSH secretion was unaffected by UFA treatment. We demonstrated in LβT2 cells that linoleate effect is mediated neither by activation of membrane fatty acid (FA) receptors GPR40 or GPR120 although we characterized these receptors in LβT2 cells, nor through nuclear peroxisome proliferator-activated receptors. Furthermore, linoleate β-oxidation is not required for its action on LH secretion. In contrast, pharmacological inhibition of protein kinase C (PKC) or ERK pathways significantly prevented linoleate-stimulated LH release. Accordingly, linoleate was shown to activate novel PKC isoforms, PKCε and -θ, as well as ERK1/2 in LβT2 cells. Lastly, unsaturated, but not saturated, FA inhibited GnRH-induced LH secretion in LβT2 cells as well as in pituitary cell cultures. Altogether, these results suggest that the pituitary is a relevant site of FA action and that UFA may influence reproduction by directly interfering with basal and GnRH-dependent gonadotrope activity.

Evidence for an increased opioid inhibition of LH secretion in hyperprolactinaemic ovariectomized rats

10.1677/joe.0.1010057 ◽

1984 ◽

Vol 101 (1) ◽

pp. 57-61 ◽

Cited By ~ 6

Author(s):

D. A. Carter ◽

J. S. Cooper ◽

S. E. Inkster ◽

S. A. Whitehead

Keyword(s):

Positive Feedback ◽

Day Treatment ◽

Inhibitory Effect ◽

Ovariectomized Rats ◽

Dopamine Antagonist ◽

Similar Treatment ◽

Lh Surge ◽

Lh Release ◽

Ovine Prolactin ◽

ABSTRACT The effects of acute and sub-chronic hyperprolactinaemia on the positive feedback action of progesterone in oestrogen-primed ovariectomized rats have been compared. A single injection of ovine prolactin administered with progesterone had no effect on the LH surge measured 5 h later although hyperprolactinaemia induced by 5-day treatment with the dopamine antagonist, domperidone, markedly attenuated the surge. Repeated injections of naloxone (5 mg/kg) during the development of the progesterone-stimulated LH surge completely reversed this inhibitory effect of hyperprolactinaemia, but had no apparent effect on the positive feedback action in control animals. In oestrogen-primed animals similar treatment with naloxone (0·4 and 5 mg/kg) stimulated LH secretion but the increase was significantly smaller than that observed after injecting progesterone. It is suggested that hyperprolactinaemia increases the inhibitory opioid modulation of LH release and that this effect is responsible for the impairment of the positive feedback action of progesterone. J. Endocr. (1984) 101, 57–61

Prolactin- and testosterone-induced inhibition of LH secretion after orchidectomy: role of catecholaminergic neurones terminating in the diagonal band of Broca, medial preoptic nucleus and median eminence

10.1677/joe.0.1480291 ◽

1996 ◽

Vol 148 (2) ◽

pp. 291-301 ◽

Cited By ~ 12

Author(s):

S-K Park ◽

D A Strouse ◽

M Selmanoff

Keyword(s):

Median Eminence ◽

Inhibitory Effect ◽

Male Rats ◽

Testosterone Replacement ◽

Preoptic Nucleus ◽

Medial Preoptic Nucleus ◽

Diagonal Band ◽

Lh Release ◽

Diagonal Band Of Broca ◽

Abstract Central catecholaminergic neurones projecting to specific hypothalamic structures are involved in stimulating and inhibiting the activity of the GnRH-containing neurosecretory neurones. Both testosterone and elevated circulating prolactin (PRL) levels inhibit postcastration LH release. Three groups of adult male rats were orchidectomized and adrenalectomized, received corticosterone replacement and were: (i) administered purified ovine PRL (oPRL; 2400 μg/s.c. injection) or (ii) its diluent, polyvinylpyrrolidone (PVP), every 12 h, or (iii) received physiological testosterone replacement for 2 days. At 0, 2 and 6 days postcastration, norepinephrine (NE), epinephrine (E) and dopamine (DA) turnover were estimated by the α-methyl-p-tyrosine method in three micro-dissected hypothalamic structures: the diagonal band of Broca at the level of the organum vasculosum of the lamina terminalis (DBB(ovlt)), the medial preoptic nucleus (MPN) and the median eminence (ME). In control (PVP-treated) rats, serum LH concentrations increased eightfold at 2 and 6 days postcastration and this rise was prevented by testosterone. oPRL treatment transiently suppressed LH secretion at 2 but not 6 days postcastration. Castration significantly decreased basal rat PRL (rPRL) levels at 2 and 6 days and testosterone administration partially prevented this effect. NE turnover in the ME and E turnover in the MPN increased markedly at 2 and 6 days postcastration, and testosterone replacement for 2 days prevented these increases. Thus, noradrenergic neurones innervating the ME and adrenergic neurones innvervating the MPN may drive postcastration LH secretion by providing stimulatory afferent input to the GnRH neurones. It was striking to observe that oPRL blocked the increases in both ME NE and MPN E turnover at 2 but not 6 days postcastration. Hence, oPRL may transiently suppress LH release by an inhibitory action on these NE and E neurones. DA turnover in the DBB(ovlt) was significantly decreased by 6 days postcastration. Testosterone-treated (2 days postcastration) and oPRL-treated (2 and 6 days postcastration) rats exhibited turnover values indistinguishable from day 0 controls. Hence, the A14 dopaminergic neurones, which synapse on GnRH neurones in the rostral preoptic area and may exert an inhibitory effect on them, are positively regulated by PRL and perhaps by testosterone as well. Autoregulatory feedback suppression of endogenous rPRL secretion by oPRL was observed both 2 and 6 days postcastration. In contrast to the A14 dopaminergic neurones, turnover in the A12 tuberoinfundibular dopaminergic (TIDA) neurones innervating the ME increased significantly by 6 days postcastration in control rats while oPRL administration further increased ME DA turnover at both 2 and 6 days. Hence, autofeedback regulation of rPRL secretion persists through at least 6 days of oPRL exposure temporally associated with markedly increased turnover in the TIDA neurones. In summary, our results support the hypothesis that the inhibitory effect of PRL on postcastration LH release is mediated by suppression of the activity of NE neurones innervating the ME and E neurones terminating in the MPN which, with time, become refractory to continued PRL exposure. Journal of Endocrinology (1996) 148, 291–301

Ovarian stimulation with FSH reduces phosphorylation of gonadotrope progesterone receptor and LH secretion in the rat

Reproduction ◽

10.1530/rep-08-0318 ◽

2009 ◽

Vol 137 (1) ◽

pp. 151-159 ◽

Cited By ~ 5

Author(s):

Ana Gordon ◽

José C Garrido-Gracia ◽

Rafaela Aguilar ◽

Silvia Guil-Luna ◽

Yolanda Millán ◽

...

Keyword(s):

Progesterone Receptor ◽

Ovarian Stimulation ◽

Inhibitory Effect ◽

Ovx Rats ◽

Formalin Fixed Paraffin ◽

Formalin Fixed Paraffin Embedded ◽

Experimental Approaches ◽

Lh Release ◽

Administration of human FSH (hFSH) to cyclic rats during the dioestrous phase attenuates progesterone receptor (PR)-dependent events of the preovulatory LH surge in pro-oestrus. The increased bioactivity of the putative ovarian gonadotropin surge inhibiting/attenuating factor induced by hFSH treatment is not associated with a decrease in PR protein expression, and the possibility of its association at a PR posttranslational effect has been raised. The present experiments aimed to analyse PR phosphorylation status in the gonadotrope of rats with impaired LH secretion induced byin vivohFSH injection. Two experimental approaches were used. First, incubated pro-oestrous pituitaries from hFSH-injected cycling and oestrogen-treated ovariectomized (OVX) rats were used to analyze the effect of calyculin, an inhibitor of intracellular phosphatases, on PR-dependent LH release, which was measured in the incubation medium by RIA. Second, pituitaries taken from hFSH-injected intact cycling and OVX rats and later incubated with P or GNRH1 were used to assess the phosphorylation rate of gonadotrope. The latter was analysed in formalin-fixed, paraffin-embedded tissue sections by immunohistochemistry using a MAB that recognizes the phosphorylated (p) form of PR at Ser294. Calyculin reduced the ovary-mediated inhibition of hFSH in GNRH1-stimulated LH secretion. In addition, the immunohistochemical expression of pSer294 PR was significantly reduced after ovarian stimulation with hFSH in pituitaries from pro-oestrous rats incubated with P or GNRH1. Altogether, these results suggested that the ovarian-dependent inhibitory effect of FSH injection on the preovulatory LH secretion in the rat may involve an increase in dephosphorylation of PR.

Suppression of LH response to gonadotrophin-releasing hormone or oestradiol by ACTH(1–24) treatment in anoestrous ewes

10.1677/joe.0.1180193 ◽

1988 ◽

Vol 118 (2) ◽

pp. 193-197 ◽

Cited By ~ 19

Author(s):

H. Dobson ◽

S. A. Essawy ◽

M. G. S. Alam

Keyword(s):

Plasma Concentrations ◽

Suppressive Effect ◽

Reproductive Efficiency ◽

Adrenocorticotrophic Hormone ◽

Releasing Hormone ◽

Oestradiol Benzoate ◽

Lh Release ◽

Gonadotrophin Releasing Hormone ◽

Baseline Values ◽

ABSTRACT Stress is known to result in lowered female reproductive efficiency. The objective of this study was to examine how increased pituitary-adrenal activity may influence gonadotrophin release in anoestrous ewes. Various doses (0·06–1·0 mg) of a synthetic adrenocorticotrophic hormone (ACTH(1–24)) preparation were injected into ewes 30 min or 3 h before an i.v. injection of 500 ng gonadotrophin-releasing hormone (GnRH). The LH response to GnRH given 30 min after ACTH(1–24) was similar to that after GnRH alone, whereas the response 3 h after ACTH(1–24) was significantly lower, irrespective of the dose of ACTH(1–24). At 30 min and 3 h after ACTH(1–24) the concentrations of cortisol exceeded 50 nmol/l compared with baseline values of < 10 nmol/l. The effect of ACTH(1–24) on oestradiol-induced LH release was also examined. Those ewes receiving 0·8 mg ACTH(1–24) depot and 50 μg oestradiol benzoate simultaneously had a preovulatory-type increase in LH 14–20 h later, similar to when oestradiol benzoate was given alone. None of the ewes receiving an additional 0·8 mg ACTH(1–24) depot 10 h after oestradiol benzoate had increases in LH concentration. The cortisol concentrations in all ewes receiving either one or two injections of ACTH(1–24) were > 35 nmol/l at 10 h after the oestradiol injection. However, concentrations of progesterone increased from 0·9 ± 0·3 (s.e.m.) nmol/l at the time of the second ACTH(1–24) injection to 2·1 ±0·3 nmol/l after 2 h. In summary, it would appear that the suppressive effect of ACTH(1–24) on LH secretion induced by GnRH or oestradiol in the anoestrous ewe is not dependent on increased plasma concentrations of cortisol. J. Endocr. (1988) 118, 193–197

Inhibition of the secretion of LH in ovariectomised pigs by sustained but not repeated acute elevation of cortisol in the absence but not the presence of oestradiol

10.1677/joe.0.1630477 ◽

1999 ◽

Vol 163 (3) ◽

pp. 477-486 ◽

Cited By ~ 20

Author(s):

AI Turner ◽

PH Hemsworth ◽

BJ Canny ◽

AJ Tilbrook

Keyword(s):

Acute Stress ◽

Plasma Concentrations ◽

Pulse Amplitude ◽

Follicular Phase ◽

Elevated Plasma ◽

Acute Elevation ◽

The Mean ◽

The Impact ◽

Lh Secretion ◽

Prolonged Stress

Prolonged stress is known to impair reproduction. It has been proposed that reproduction will also be impaired when a severe acute stress occurs during a period of elevated plasma concentrations of oestradiol, such as during the follicular phase of the oestrous cycle. In this experiment, we hypothesised that repeated acute and sustained elevation of cortisol would suppress the secretion of LH in ovariectomised pigs and that these effects would be enhanced in the presence of oestradiol negative feedback. Cortisol (or vehicle) was administered 12 hourly to ovariectomised pigs (n=6/treatment) for 8 days in the absence of oestradiol treatment and for a further 8 days during treatment with oestradiol. Vehicle was administered to 'control' pigs, 10 or 20 mg cortisol was administered i.v. to pigs to produce 'repeated acute' elevation of cortisol and 250 mg cortisol was administered i.m. to pigs to give a 'sustained' elevation of cortisol. Both before and during treatment with oestradiol, plasma concentrations of LH were monitored on the day before treatment, on the 4th and 8th days of treatment and following an i.v. injection of GnRH at the end of the 8th day of treatment. The repeated acute elevation of cortisol did not impair any parameters of LH secretion (i.e. mean plasma concentrations of LH, pulse amplitude or frequency, pre-LH pulse nadir or the LH response to GnRH) in the absence or in the presence of oestradiol. In contrast, when the elevation of cortisol was sustained, the mean plasma concentrations of LH and the pre-LH pulse nadir were significantly (P<0.05) lower on the 8th day of treatment than on the day before treatment and on the 4th day of treatment. Nevertheless, no other parameters of LH secretion were affected and these effects only occurred in the absence (not in the presence) of oestradiol. In conclusion, cortisol needed to be elevated for more than 4 days to impair the secretion of LH, and oestradiol did not enhance the impact of cortisol on LH secretion in ovariectomised pigs.

Cholinergic inputs to the amygdala and the control of gonadotrophin release

Acta Endocrinologica ◽

10.1530/acta.0.0930001 ◽

1980 ◽

Vol 93 (1) ◽

pp. 1-6 ◽

Cited By ~ 13

Author(s):

Flavio Piva ◽

José Borrell ◽

Patrizia Limonta ◽

Gilberto Gavazzi ◽

Luciano Martini

Keyword(s):

Nicotinic Receptors ◽

Serum Levels ◽

Inhibitory Effect ◽

Female Rats ◽

Muscarinic Agonist ◽

Time Intervals ◽

Gonadotrophin Secretion ◽

Lh Release ◽

Lh Secretion ◽

Cholinomimetic Drugs

Abstract. Adult female rats castrated 4 weeks before were implanted bilaterally into the basomedial area of the amygdala with drugs known to mimic or to counteract the actions of acetylcholine. The animals were sacrificed at different time intervals after the implantation of the different compounds, and serum levels of LH and FSH were measured by radioimmunoasay. The data obtained indicate that the intra-amygdalar implantation of the muscarinic blocker atropine induces a significant increase of the release of LH without altering FSH secretion. The implantation of two cholinomimetic drugs, pilocarpine, an almost pure muscarinic agonist, and carbachol, which possesses both muscarinic and nicotinic properties, exerted an inhibitory effect only on LH release. On the contrary, the intra-amygdalar placement of the nicotinic blocker mecamylamine was followed by an increase of FSH with no changes in LH. These observations may suggest that cholinergic signals reaching the amygdala may be of some relevance in the mechanisms controlling gonadotrophin secretion. Muscarinic receptors seem to play an inhibitory role in the regulation of LH secretion, while nicotinic receptors seem to modulate in an inhibitory way FSH release.

No Evidence That RFamide-Related Peptide 3 Directly Modulates LH Secretion in the Ewe

Endocrinology ◽

10.1210/en.2015-1854 ◽

2016 ◽

Vol 157 (4) ◽

pp. 1566-1575 ◽

Cited By ~ 26

Author(s):

C. Decourt ◽

K. Anger ◽

V. Robert ◽

D. Lomet ◽

J. Bartzen-Sprauer ◽

...

Keyword(s):

Receptor Antagonist ◽

Estradiol Benzoate ◽

Inhibitory Effect ◽

Minor Role ◽

Gonadotropin Secretion ◽

Related Peptide ◽

Lh Pulsatility ◽

Lh Release ◽

A Minor ◽

Abstract The neuropeptide RFamide-related peptide 3 (RFRP-3) has been implicated in the control of gonadotropin secretion in both birds and mammals. However, in mammals, depending on species, sex and photoperiod, inhibitory, excitatory, or no effect of RFRP-3 on the plasma concentration of LH has been reported. In the ewe, treatment with RFRP-3 either reduced LH concentration or had no effect, and treatment with an RFRP-3 receptor antagonist (ie, RF9) resulted in increased concentration of plasma LH. To clarify these conflicting results in the present study, a set of experiments was performed in ewes. Multiple iv injections of RFRP-3 (6 × 50 μg) in ovariectomized ewes had no effect on plasma LH pulsatility. In intact ewes a bolus injection (500 μg) or an injection (250, 500, or 1000 μg) followed by a 4-hour perfusion (250, 500, or 1000 μg · h−1) of RFRP-3 had no effect on the LH pulse induced by kisspeptin (6.5 μg). In ovariectomized, estrogen-replaced ewes, the LH surge induced by estradiol benzoate was not modified by a 24-hour perfusion of RFRP-3 (500 μg h−1). Finally, although treatment with RF9 induced a robust release of LH, treatment with a more selective RFRP-3 receptor antagonist, GJ14, resulted in no evident increase of LH. In contrast to the inhibitory effect previously suggested, our data are more consistent with the concept that RFRP-3 has no direct effect on LH secretion in ewes and that RF9 effect on LH release is likely not RFRP-3 receptor mediated. Hence, RFRP-3 probably has a minor role on the control of LH secretion in the ewe.

Effects of non-steroidal gonadal factors on LH secretion in female common carp during the reproductive cycle

Czech Journal of Animal Science ◽

10.17221/337-cjas ◽

2008 ◽

Vol 53 (No. 9) ◽

pp. 398-403

Author(s):

J. Chyb ◽

T. Mikolajczyk ◽

M. Sokolowska-Mikolajczyk ◽

M. Socha ◽

P. Szczerbik ◽

...

Keyword(s):

Common Carp ◽

Reproductive Cycle ◽

Inhibitory Effect ◽

Gonad Maturity ◽

Lh Release ◽

Gonadal Recrudescence ◽

The aim of this study was to evaluate the effects of recombinant human inhibin A, recombinant human activin A and desteroidized ovarian extract on LH secretion in vitro and in vivo in female common carp during different stages of reproductive cycle. Inhibin stimulated spontaneous as well as GnRH-stimulated LH release in vivo in fish during gonadal recrudescence. This hormone did not have an influence on spontaneous LH secretion in the periovulatory period, but had a slightly inhibitory effect on GnRH-stimulated LH release in this stage of gonad maturity. Activin decreased spontaneous LH secretion during gonadal recrudescence and increased LH secretion before ovulation, having no effects on GnRH-stimulated LH release during both stages of gonad maturity. The desteroidized ovarian extract failed to modify spontaneous LH secretion, but decreased GnRH-stimulated LH release during recrudescence and especially before ovulation. It is to conclude that these data suggest the differential role of inhibin/activin as substances in the regulation of LH secretion in common carp females.

Effect of small doses of bovine follicular fluid on the tonic secretion of gonadotrophins in the ewe

10.1677/joe.0.1140073 ◽

1987 ◽

Vol 114 (1) ◽

pp. 73-79 ◽

Cited By ~ 14

Author(s):

G. B. Martin ◽

P. L. Taylor ◽

A. S. McNeilly

Keyword(s):

Follicular Fluid ◽

Plasma Concentrations ◽

Pulse Amplitude ◽

Inhibitory Effect ◽

Detectable Effect ◽

Pulse Interval ◽

High Dose ◽

Small Doses ◽

ABSTRACT Previous work has shown that treatment of ewes with steroid-free bovine follicular fluid (bFF), a rich source of inhibin, partially inhibits the increase in mean plasma concentrations of LH induced by ovariectomy. The present experiment was designed to test the hypothesis that this effect was a reflection of reduced LH pulse amplitude which would only be expressed at high (pharmacological) doses of bFF. To do this, we assessed the dose–response to bFF of the secretion of FSH and LH pulses in intact and acutely ovariectomized ewes. In intact ewes, a low dose of bFF (0·2 ml s.c. every 8 h) had no detectable effect on the secretion of FSH, an intermediate dose (0·6 ml s.c. every 8 h) depressed FSH concentrations for about 24 h and a high dose (1·8 ml s.c. every 8 h) reduced FSH concentrations to undetectable levels. In ewes treated with 1·8 ml bFF, FSH concentrations also remained undetectable after ovariectomy and did not increase until treatment was withdrawn. In ewes treated with 0·6 ml bFF, FSH concentrations were maintained at normal intact levels for about 32 h following ovariectomy but then rose to normal ovariectomized levels. In ewes treated with 0·2 ml bFF, FSH concentrations increased immediately after ovariectomy but more slowly than in control ovariectomized ewes. Profiles of LH pulses were recorded after ovariectomy, during and after the withdrawal of bFF treatment. In ewes treated with the highest dose (1·8 ml s.c. every 8 h), mean LH levels and pulse amplitude were lower than in control ewes and increased significantly following withdrawal of treatment. None of the other pulse variables measured (apparent half-life, pulse interval, nadir) were significantly affected. The lower doses did not significantly affect LH secretion. It was concluded that FSH secretion can be inhibited for short periods by low doses of inhibin and that a dose of 0·6 ml bFF every 8 h is approximately equivalent to normal ovarian output. However, another factor, possibly oestrogen, is also involved in the long-term regulation of plasma FSH concentrations. The inhibitory effect of bFF on LH pulse amplitude was only observed at the highest dose, suggesting that it is a pharmacological effect and that it is unlikely that inhibin plays a major role in the control of tonic LH secretion. J. Endocr. (1987) 114, 73–79