Ghrelin suppresses the GnRH-induced preovulatory gonadotropin surge in dairy heifers

Chouzouris, Thomas-Markos; Dovolou, Eleni; Dafopoulos, Konstantinos; Georgoulias, Panagiotis; Vasileiou, N.G.C.; Fthenakis, G.C.; Anifandis, George; Amiridis, G.S.

doi:10.1016/j.theriogenology.2016.05.022

Cited by 19 publications

(18 citation statements)

References 56 publications

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“…For example, the KGN cell line used in this study was originally from a 63-years old woman [69] and thus it may not represent the same granulosa cells from the other aged ovaries. Regardless, in addition to our current findings of ghrelin in ovarian inflammation, previous studies have already revealed various impacts of ghrelin in the reproductive system [19,20,21,22,23,24,25,26,27]. Thus, there is a possibility that ghrelin administration might be a potential strategy to treat inflammation-related diseases in reproductive tissues.…”

Section: Discussionsupporting

confidence: 70%

“…Human ghrelin was also demonstrated to reduce the pituitary response to gonadotropin-releasing hormone (GnRH) in superovulated ewes [24]. Ghrelin was shown to improve the bovine blastocyst formation [25] and to enhance the maturation of bovine oocytes [26], but it was also reported to inhibit the GnRH-induced preovulatory gonadotropin surge in dairy heifers [27]. Accumulated findings from these studies indicate that ghrelin may play an important role in the ovarian system.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Growth Hormone Releasing Peptide-2 Attenuation of Protein Kinase C-Induced Inflammation in Human Ovarian Granulosa Cells

Chao

Sun

Peng

et al. 2016

IJMS

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Cyclooxygenase-2 (COX-2) and interleukin-8 (IL-8) are two important inflammatory mediators in ovulation. Ghrelin may modulate inflammatory signaling via growth hormone secretagogue receptors. We investigated the role of ghrelin in KGN human ovarian granulosa cells using protein kinase C (PKC) activator phorbol 12, 13-didecanoate (PDD) and synthetic ghrelin analog growth hormone releasing peptide-2 (GHRP-2). GHRP-2 attenuated PDD-induced expression of protein and mRNA, the promoter activity of COX-2 and IL-8 genes, and the secretion of prostaglandin E2 (PGE2) and IL-8. GHRP-2 promoted the degradation of PDD-induced COX-2 and IL-8 proteins with the involvement of proteasomal and lysosomal pathways. PDD-mediated COX-2 production acts via the p38, c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways; PDD-mediated IL-8 production acts via the p38, JNK and ERK pathways. GHRP-2 reduced the PDD-induced phosphorylation of p38 and JNK and activator protein 1 (AP-1) reporter activation and PDD-induced NF-κB nuclear translocation and reporter activation. The inhibitors of mitogen-activated protein kinase phosphatase-1 (MKP-1) and protein phosphatase 2 (PP2A) reduced the inhibitory effect of GHRP-2 on PDD-induced COX-2 and IL-8 expression. Our findings demonstrate an anti-inflammatory role for ghrelin (GHRP-2) in PKC-mediated inflammation of granulosa cells, at least in part, due to its inhibitory effect on PKC-induced activation of p38, JNK and NF-κB, possibly by targeting to MKP-1 and PP2A.

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Section: Discussionsupporting

confidence: 70%

Section: Introductionmentioning

confidence: 99%

Growth Hormone Releasing Peptide-2 Attenuation of Protein Kinase C-Induced Inflammation in Human Ovarian Granulosa Cells

Chao

Sun

Peng

et al. 2016

IJMS

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“…The results in animals are more consistent than those in humans with the majority of the studies showing a central inhibitory action of ghrelin on GnRH and/or gonadotrophin secretion . Recently, a suppressive effect of ghrelin on GnRH‐induced luteinizing hormone (LH) and follicle‐stimulating hormone (FSH) secretion has been demonstrated in ewes and heifers after the iv administration of this hormone …”

Section: Introductionsupporting

confidence: 55%

“…[4][5][6][7][8] Recently, a suppressive effect of ghrelin on GnRH-induced luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion has been demonstrated in ewes and heifers after the iv administration of this hormone. 9,10 Human research regarding the role of ghrelin in gonadotrophin secretion has provided inconsistent results. Studies in men have demonstrated that the acute injection of a high dose or the administration of multiple small doses of ghrelin shows, respectively, either no effect 2 or a suppressive action on gonadotrophin levels.…”

mentioning

confidence: 99%

Submaximal doses of ghrelin do not inhibit gonadotrophin levels but stimulate prolactin secretion in postmenopausal women

Messini

Malandri

Anifandis

et al. 2017

Clinical Endocrinology

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“…Studies conducted in rats, rhesus monkeys, sheep and cows have demonstrated that ghrelin administration attenuates LH secretion (Fernández‐Fernández, Tena‐Sempere, Aguilar, & Pinilla, ; Iqbal, Kurose, Canny, & Clarke, ; Vulliémoz et al, ). In previous studies, we provided evidence that peripherally administered acylated ghrelin inhibits the GnRH‐induced preovulatory surge of LH and FSH both in cattle and sheep (Chouzouris et al, ; Dovolou et al, ). Further, we have shown that acylated ghrelin accelerates in vitro oocyte maturation, reduces blastocyst formation rate and alters the expression of many genes related to metabolism, glucose utilization, oxidation, placentation and apoptosis in oocytes, cumulus cells and embryos (Chouzouris et al, ; Dovolou, Messinis, et al, ; Dovolou, Periquesta, et al, ).…”

Section: Introductionmentioning

confidence: 95%

A study on ghrelin and LH secretion after short fasting and on ghrelin levels at perioestrual period in dairy cattle

Chouzouris

Dovolou

Rekkas³

et al. 2018

Reprod Domestic Animals

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In two experiments, we studied (a) the changes of LH secretion in heifers under different feeding schedules and (b) total ghrelin concentration at oestrus in cows and heifers. In experiment one, synchronized heifers were allocated in three groups (R, regularly fed controls; F, fasted; and F-F fasted-fed). One day after the completion of the oestrous induction protocol, group F and F-F animals stayed without feed for 24 hr; thereafter, feed was provided to R and F-F cattle; 2 hr later, GnRH was administered to all animals. Blood samples were collected for ghrelin, progesterone, LH and cortisol concentrations. Fasting caused increased ghrelin concentrations in groups F and F-F, while in response to GnRH, LH surge was significantly attenuated in groups F and F-F compared to R. In experiment 2, lactating cows and heifers were used. On day 9 of a synchronized cycle, PGF2α was administered, and blood samples were collected twice daily until the third day after oestrus and analysed for progesterone, estradiol, ghrelin, glucose and BHBA concentrations. No difference was recorded between groups in steroids and BHBA concentrations. In comparison to mid-luteal values, ghrelin concentrations significantly increased at perioestrual period in cows, but not in heifers. This study provides evidence that starving-induced elevated ghrelin concentrations can have suppressing effect on LH secretion, even after ghrelin's restoration to basal values and that during oestrus, ghrelin secretion is differently regulated in cows and heifers, likely being independent from oestradiol concentrations. Further research is required to identify the determining factors that drive the different regulation of ghrelin secretion in cows and heifers.

show abstract

Ghrelin suppresses the GnRH-induced preovulatory gonadotropin surge in dairy heifers

Cited by 19 publications

References 56 publications

Growth Hormone Releasing Peptide-2 Attenuation of Protein Kinase C-Induced Inflammation in Human Ovarian Granulosa Cells

Growth Hormone Releasing Peptide-2 Attenuation of Protein Kinase C-Induced Inflammation in Human Ovarian Granulosa Cells

Submaximal doses of ghrelin do not inhibit gonadotrophin levels but stimulate prolactin secretion in postmenopausal women

A study on ghrelin and LH secretion after short fasting and on ghrelin levels at perioestrual period in dairy cattle

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