KiSS-1 in the mammalian ovary: distribution of kisspeptin in human and marmoset and alterations in KiSS-1 mRNA levels in a rat model of ovulatory dysfunction

Gaytán, Francisco; Gaytán, María; Castellano, Juan Manuel Parreño; Martín‐Romero, María T.; Roa, Juan; Aparicio, Belén; Garrido, Nicolás; Sánchez-Criado, José E.; Millar, Robert P.; Pellicer, A.; Fraser, Hamish M.; Tena‐Sempere, Manuel

doi:10.1152/ajpendo.90895.2008

Cited by 152 publications

(124 citation statements)

References 52 publications

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“…In the same experiment, we observed an increase in total number of corpora lutea with an increase in newly generated (R850 mm) corpora lutea, those that can correspond to the recently ovulated follicles, indicating that high KP conducts a higher proportion of large antral follicles to ovulation. This finding coincides with the fact that KP expression in the ovary increases specifically in late proestrus (Castellano et al 2006) and also increases in response to human chorionic gonadotrophin (hCG) stimulation in a transient manner (Gaytan et al 2009). Moreover, if ovulation is blocked by indomethacin, the induction of KP by hCG is prevented, indicating the close participation of KP in ovulation (Gaytan et al 2009).…”

Section: Kp and Ovulationsupporting

confidence: 79%

“…Previously, we showed that the in vivo administration of a KP antagonist (P234) to the ovarian bursa of 22-to 50-day-old rats delayed vaginal opening and decreased the percentage of estrous cyclicity (Ricu et al 2012). These results supported a role for locally produced ovarian KP in the ovulatory process (Gaytan et al 2009). In contrast, rat luteal cells stimulated in vitro with KP secreted progesterone via ERK1/2 signaling (Peng et al 2013).…”

Section: Introductionmentioning

confidence: 60%

“…and its receptors are expressed in the ovaries (Castellano et al 2006, Gaytan et al 2009, Ricu et al 2012, we wanted to assess whether KP directly regulates the ovarian follicular development of senescent rats through a paracrine mechanism. Interestingly, we found that ovarian KP expression increased with aging and was correlated with an increase in norepinephrine release.…”

Section: Discussionmentioning

confidence: 99%

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Kisspeptin is involved in ovarian follicular development during aging in rats

Fernandois¹,

Na²,

Cuevas³

et al. 2015

Journal of Endocrinology

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We have previously reported that kisspeptin (KP) may be under the control of the sympathetic innervation of the ovary. Considering that the sympathetic activity of the ovary increases with aging, it is possible that ovarian KP also increases during this period and participates in follicular development. To evaluate this possibility, we determined ovarian KP expression and its action on follicular development during reproductive aging in rats. We measured ovarian KP mRNA and protein levels in 6-, 8-, 10-and 12-month-old rats. To evaluate follicular developmental changes, intraovarian administration of KP or its antagonist, peptide 234 (P234), was performed using a mini-osmotic pump, and to evaluate FSH receptor (FSHR) changes in the senescent ovary, we stimulated cultured ovaries with KP, P234 and isoproterenol (ISO). Our results shows that KP expression in the ovary was increased in 10-and 12-month-old rats compared with 6-month-old rats, and this increase in KP was strongly correlated with the increase in ovarian norepinephrine observed with aging. The administration of KP produced an increase in corpora lutea and type III follicles in 6-and 10-month-old rats, which was reversed by P234 administration at 10 months. In addition, KP decreased the number and size of antral follicles in 6-and 10-month-old rats, while P234 administration produced an increase in these structures at the same ages. In ovarian cultures KP prevented the induction of FSHR by ISO. These results suggest that intraovarian KP negatively participates in the acquisition of FSHR, indicating a local role in the regulation of follicular development and ovulation during reproductive aging.

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Section: Kp and Ovulationsupporting

confidence: 79%

Section: Introductionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 99%

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Kisspeptin is involved in ovarian follicular development during aging in rats

Fernandois¹,

Na²,

Cuevas³

et al. 2015

Journal of Endocrinology

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“…Equally, it is noted in Kiss1-Cre LepR flox/flox mice that LepR deletion was also apparent in the ovary and testes . Kiss1 expression has been documented in the gonads (Gaytan et al 2009, Tariq et al 2013 and also other brain regions during development (Gottsch et al 2011), so the specificity of LepR deletion may be compromised. This, paired with the possibility of developmental compensatory mechanisms in the transgenic model, should not be ignored.…”

Section: Leptinmentioning

confidence: 99%

Kisspeptin and energy balance in reproduction

Bond¹,

Smith²

2014

Reproduction

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Kisspeptin is vital for the neuroendocrine regulation of GNRH secretion. Kisspeptin neurons are now recognized as a central pathway responsible for conveying key homeostatic information to GNRH neurons. This pathway is likely to mediate the well-established link between energy balance and reproductive function. Thus, in states of severely altered energy balance (either negative or positive), fertility is compromised, as is Kiss1 expression in the arcuate nucleus. A number of metabolic modulators have been proposed as regulators of kisspeptin neurons including leptin, ghrelin, pro-opiomelanocortin (POMC), and neuropeptide Y (NPY). Whether these regulate kisspeptin neurons directly or indirectly will be discussed. Moreover, whether the stimulatory role of leptin on reproduction is mediated by kisspeptin directly will be questioned. Furthermore, in addition to being expressed in GNRH neurons, the kisspeptin receptor (Kiss1r) is also expressed in other areas of the brain, as well as in the periphery, suggesting alternative roles for kisspeptin signaling outside of reproduction. Interestingly, kisspeptin neurons are anatomically linked to, and can directly excite, anorexigenic POMC neurons and indirectly inhibit orexigenic NPY neurons. Thus, kisspeptin may have a direct role in regulating energy balance. Although data from Kiss1r knockout and WT mice found no differences in body weight, recent data indicate that kisspeptin may still play a role in food intake and glucose homeostasis. Thus, in addition to regulating reproduction, and mediating the effect of energy balance on reproductive function, kisspeptin signaling may also be a direct regulator of metabolism.

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“…Additional actions of kiss1 at the level of the ovaries have been suggested [3][4][5][6] but remain scarcely studied. Recent data have shown that the intraovarian kiss1 system is required for properly coordinated ovarian function in humans and animals [3][4][5][6]. For example, kiss1r hypomorph (i.e., gene with reduced level of activity) mice displayed a premature decline in ovulatory rate, followed by progressive loss of antral follicles, oocyte loss, and a reduction in all categories of pre-antral follicles [3].…”

Section: Introductionmentioning

confidence: 99%

Ovarian kisspeptin expression is related to age and to monocyte chemoattractant protein-1

Merhi

Thornton

Bonney

et al. 2016

J Assist Reprod Genet

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Purpose The objective of this study was to test the hypothesis that ovarian kisspeptin (kiss1) and its receptor (kiss1r) expression are affected by age, obesity, and the age-and obesityrelated chemokine monocyte chemoattractant protein-1 (MCP-1). Methods Ovaries from reproductive-aged and older C57BL/ 6J mice fed normal chow (NC) or high-fat (HF) diet, ovaries from age-matched young MCP-1 knockout and young control mice on NC, and finally, cumulus and mural granulosa cells (GCs) from women who underwent in vitro fertilization (IVF) were collected. Kiss1, kiss1r, anti-Mullerian hormone (AMH), and AMH receptor (AMHR-II) messenger RNA (mRNA) expression levels were quantified using real-time polymerase chain reaction (RT-PCR).Results In mouse ovaries, kiss1 and kiss1r mRNA levels were significantly higher in old compared to reproductive-aged mice, and diet-induced obesity did not alter kiss1 or kiss1r mRNA levels. Compared to young control mice, young MCP-1 knockout mice had significantly lower ovarian kiss1 mRNA but significantly higher AMH and AMHR-II mRNA levels. In human cumulus GCs, kiss1r mRNA levels were positively correlated with age but not with BMI. There was no expression of kiss1 mRNA in either cumulus or mural GCs. Conclusion These data suggest a possible age-related physiologic role for the kisspeptinergic system in ovarian physiology. Additionally, the inflammatory MCP-1 may be associated with kiss1 and AMH genes, which are important in ovulation and folliculogenesis, respectively.

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KiSS-1 in the mammalian ovary: distribution of kisspeptin in human and marmoset and alterations in KiSS-1 mRNA levels in a rat model of ovulatory dysfunction

Abstract: Tena-Sempere M. KiSS-1 in the mammalian ovary: distribution of kisspeptin in human and marmoset and alterations in KiSS-1 mRNA levels in a rat model of ovulatory dysfunction. Am J Physiol Endocrinol Metab 296: E520 -

Cited by 152 publications

References 52 publications

Kisspeptin is involved in ovarian follicular development during aging in rats

Kisspeptin is involved in ovarian follicular development during aging in rats

Kisspeptin and energy balance in reproduction

Ovarian kisspeptin expression is related to age and to monocyte chemoattractant protein-1

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