Intratesticular action of kisspeptin in rhesus monkey (<i>Macaca mulatta</i>)

Irfan, Shahzad; Ehmcke, Jens; Wahab, Fazal; Shahab, Muhammad; Schlatt, Stefan

doi:10.1111/and.12121

Cited by 32 publications

(26 citation statements)

References 28 publications

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“…The pituitary, which is vital in the control of metabolic homeostasis and reproduction, highly expresses Rfrp, GnIHR, Kiss1, and Kiss1r (Lee et al 1996, Muir et al 2001, Ohtaki et al 2001, Shahab et al 2005, Ubuka et al 2009b, Smith et al 2010a,b, Tsutsui et al 2010, Wahab et al 2011a, Cejudo Roman et al 2012, Irfan et al 2014.…”

Section: Kp and Gnih Signaling In Conditions Of Altered Energy Balancmentioning

confidence: 99%

“…These organs are crucial for the maintenance of metabolic homeostasis. Likewise, these genes are also expressed in the primary sex organs, ovaries, and testes, which drive reproduction (Ohtaki et al 2001, Li et al 2012, Irfan et al 2014. While the roles of GnIH-GnIHR and KP-Kiss1r in the functioning of these peripheral organs are not fully understood at present, the modulation of these organs' endocrine secretion by the administration of GnIH and KP suggests a significance of GnIH and KP expression in the periphery.…”

Section: Kp and Gnih Signaling In Conditions Of Altered Energy Balancmentioning

confidence: 99%

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The involvement of gonadotropin inhibitory hormone and kisspeptin in the metabolic regulation of reproduction

Wahab¹,

Shahab²,

Behr³

2015

Journal of Endocrinology

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Recently, kisspeptin (KP) and gonadotropin inhibitory hormone (GnIH), two counteracting neuropeptides, have been acknowledged as significant regulators of reproductive function. KP stimulates reproduction while GnIH inhibits it. These two neuropeptides seem to be pivotal for the modulation of reproductive activity in response to internal and external cues. It is well-documented that the current metabolic status of the body is closely linked to its reproductive output. However, how reproductive function is regulated by the body's energy status is less clear. Recent studies have suggested an active participation of hypothalamic KP and GnIH in the modulation of reproductive function according to available metabolic cues. Expression of KISS1, the KP encoding gene, is decreased while expression of RFRP (NPVF), the gene encoding GnIH, is increased in metabolic deficiency conditions. The lower levels of KP, as suggested by a decrease in KISS1 gene mRNA expression, during metabolic deficiency can be corrected by administration of exogenous KP, which leads to an increase in reproductive hormone levels. Likewise, administration of RF9, a GnIH receptor antagonist, can reverse the inhibitory effect of fasting on testosterone in monkeys. Together, it is likely that the integrated function of both these hypothalamic neuropeptides works as a reproductive output regulator in response to a change in metabolic status. In this review, we have summarized literature from nonprimate and primate studies that demonstrate the involvement of KP and GnIH in the metabolic regulation of reproduction.

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Section: Kp and Gnih Signaling In Conditions Of Altered Energy Balancmentioning

confidence: 99%

Section: Kp and Gnih Signaling In Conditions Of Altered Energy Balancmentioning

confidence: 99%

The involvement of gonadotropin inhibitory hormone and kisspeptin in the metabolic regulation of reproduction

Wahab¹,

Shahab²,

Behr³

2015

Journal of Endocrinology

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“…However, this reduction was not a complete inhibition of testosterone release, which suggested that the P234 did not have a robust effect. Although there have been preliminary reports of the presence of GPR54 in the monkey testis (Irfan et al, 2008;Tariq et al, 2010), initial findings from our laboratory have . a) Time course of plasma testosterone levels (mean ± SEM) before and after vehicle or P234 intravenous bolus injection (38.8 µg/kg BW; arrow) in adult male rhesus monkeys (n = 5).…”

Section: Discussionmentioning

confidence: 68%

Peripheral administration of kisspeptin antagonist does not alter basal plasma testosterone but decreases plasma adiponectin levels in adult male rhesus macaques

Huma¹,

Ulla²,

Hanif³

et al. 2014

Turk J Biol

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Kisspeptin signaling is a potent regulator of the reproductive axis and an elicitor of gonadotropin-releasing hormone secretion. The present study assessed the effect of the peripheral administration of a kisspeptin antagonist (P234) on testosterone secretion in the adult male rhesus monkey. Five monkeys were administered with either P234 (38.8 µg/kg body weight) or a vehicle (0.9% saline). Plasma testosterone and adiponectin levels, as a positive control, were then measured using specific ELISA assays from blood samples collected sequentially at 15-min intervals from 60 min prior to until 360 min after the P234/vehicle injection. In 3 monkeys, the experiment was repeated where the animals received a kisspeptin-10 (50 µg) challenge 30 min after the P234 or vehicle treatment. No effects on basal testosterone levels were found after the systemic administration of P234. Plasma adiponectin levels were found to be briefly decreased by P234. P234 administration was found to suppress kisspeptin-dependent testosterone release and to inhibit kisspeptin-dependent adiponectin release. This suggested that the systemic administration of P234 was effective peripherally. However, the minimal peripheral effects on testosterone secretion in the male macaque suggested that P234 did not cross the blood-brain barrier and blocked the peripheral kisspeptin receptors.

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“…Hence, one could speculate that this might indicate a dose-related direct effect of kisspeptin-54 at the testes. Kisspeptin-54 receptors are present in the testes, and kisspeptin-54 has been observed to significantly increase hCG-stimulated testosterone response in monkeys, consistent with a direct testicular action [37]. …”

Section: Discussionmentioning

confidence: 99%

Hypothalamic Response to Kisspeptin-54 and Pituitary Response to Gonadotropin-Releasing Hormone Are Preserved in Healthy Older Men

et al. 2018

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Background: Male testosterone levels decline by 1% per year from the age of 40 years. Whilst a primary testicular deficit occurs, hypothalamic or pituitary dysregulation may also coexist. This study aimed to compare the hypothalamic response to kisspeptin-54 and the pituitary response to gonadotropin-releasing hormone (GnRH) of older men with those of young men. Methods: Following 1 h of baseline sampling, healthy older men (n = 5, mean age 59.3 ± 2.9 years) received a 3-h intravenous infusion of either vehicle, kisspeptin-54 0.1, 0.3, or 1.0 nmol/kg/h or GnRH 0.1 nmol/kg/h, on five different study days. Serum gonadotropins and total testosterone were measured every 10 min and compared to those of young men (n = 5/group) (mean age 28.9 ± 2.0 years) with a similar body mass index (24 kg/m²) who underwent the same protocol. Results: Kisspeptin-54 and GnRH significantly stimulated serum gonadotropin release in older men compared to vehicle (p < 0.001 for all groups). Gonadotropin response to kisspeptin-54 was at least preserved in older men when compared to young men. At the highest dose of kisspeptin-54 (1.0 nmol/kg/h), a significantly greater luteinising hormone (LH) (p = 0.003) response was observed in older men. The follicle-stimulating hormone (FSH) response to GnRH was increased in older men (p = 0.002), but the LH response was similar (p = 0.38). Serum testosterone rises following all doses of kisspeptin-54 (p ≤ 0.009) were reduced in older men. Conclusions: Our data suggest that healthy older men without late-onset hypogonadism (LOH) have preserved hypothalamic response to kisspeptin-54 and pituitary response to GnRH, but impaired testicular response. Further work is required to investigate the use of kisspeptin-54 to identify hypothalamic deficits in men with LOH.

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Intratesticular action of kisspeptin in rhesus monkey (Macaca mulatta)

Cited by 32 publications

References 28 publications

The involvement of gonadotropin inhibitory hormone and kisspeptin in the metabolic regulation of reproduction

The involvement of gonadotropin inhibitory hormone and kisspeptin in the metabolic regulation of reproduction

Peripheral administration of kisspeptin antagonist does not alter basal plasma testosterone but decreases plasma adiponectin levels in adult male rhesus macaques

Hypothalamic Response to Kisspeptin-54 and Pituitary Response to Gonadotropin-Releasing Hormone Are Preserved in Healthy Older Men

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