Abstract
The neurobiological mechanism of puberty onset in primates is currently only partly understood. A recent study reported an important role of Dmx-like 2 (DMXL2), a gene encoding rabconnectin-3α vesicular protein, in human subjects with mental retardation and neuroendocrine impairment of reproduction. To further characterize the potential role of DMXL2 in the regulation of reproduction, we analyzed the expression of DMXL2 in hypothalami of newborn, infantile, juvenile, pubertal, and postpubertal female and male common marmoset monkeys. Additionally, as the relative hypothalamic levels of gonadotropin-inhibitory hormone (GnIH) transcript during postnatal development are unknown in primates, we also quantified messenger RNA (mRNA) levels of RFRP, a gene encoding GnIH. Moreover, the transcript levels of kisspeptin, a well-known regulator of the hypothalamic neurohormonal axis controlling reproduction, were also checked. Transcript and protein levels of DMXL2 and Kiss1 transcript levels increase from the newborn to the infantile and from the juvenile (prepubertal) to the pubertal and the postpubertal period. We also noted a clear upsurge in RFRP transcript levels in the prepubertal period. In conclusion, the hypothalamic expressions of Kiss1 and DMXL2 mRNA increase during infantile, pubertal, and adult stages compared to newborn and juvenile stages in common marmoset monkeys. In contrast, the expression of RFRP mRNA upsurges in juvenile monkeys. Further mechanistic studies are needed to characterize the potential inhibitory role of the GnIH-GPR147 signaling in the prepubertal period and the role of DMXL2 in the molecular cascade regulating the neuroendocrine reproductive axis in primates.
Highlights
Reproductive function is regulated by various neural and endocrine factors of the hypothalamic-pituitary-gonadal (HPG) axis [1]
There was no significant difference in Dmx-like 2 (DMXL2) protein levels between adult female and male monkeys. (*P < 0.05, **P < 0.01, ***P < 0.005; Student’s t test and one ANOVA followed by post hoc Tukey test) transcript levels significantly increase from the NB to the infantile stage (Fig. 1a; P < 0.01)
In male marmosets, DMXL2 messenger RNA (mRNA) increases from the NB to the infantile stage and from the juvenile to the pubertal and adult stage
Summary
Reproductive function is regulated by various neural and endocrine factors of the hypothalamic-pituitary-gonadal (HPG) axis [1]. Among these factors is the gonadotropin-releasing hormone (GnRH), a decapeptide secreted in a pulsatile manner by a specialized set of hypothalamic GnRH neurons. The activity of GnRH neurons is increased in the infantile stage at minipuberty—the time at which an adult-like level of gonadotropins and gonadal sex hormone levels in infants occurs —and is lowered again in the juvenile stage due to central inhibition [2, 3]. The GnRH neuronal activities again resurged in true puberty after removal of the central inhibition and remain at high levels throughout adult reproductive life [2]
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