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Regulation and Function of RFRP-3 (GnIH) Neurons during Postnatal Development.

Poling MC, Kauffman AS - Front Endocrinol (Lausanne) (2015)

Bottom Line: Here, we discuss the latest evidence relating to RFRP-3 neuron regulation and function during development and sexual maturation, focusing on rodents.We highlight significant changes in RFRP-3 and Rfrp expression, as well as RFRP-3 neuronal activation, during key stages of postnatal and pubertal development and also discuss recent evidence testing the requisite role of RFRP-3 receptors for normal pubertal timing and developmental LH secretion.Interestingly, some findings suggest that endogenous RFRP-3 signaling may not be necessary for the puberty timing, at least in some species, forcing new hypotheses to be generated regarding this peptide's functional significance to sexual maturation and development.

View Article: PubMed Central - PubMed

Affiliation: Department of Reproductive Medicine, University of California, San Diego , La Jolla, CA , USA.

ABSTRACT
RFamide-related peptide-3 (RFRP-3) [mammalian ortholog to gonadotropin-inhibiting hormone (GnIH)] potently inhibits gonadotropin secretion in mammals. Studies of RFRP-3 immunoreactivity and Rfrp expression (the gene encoding RFRP-3) in mammalian brains have uncovered several possible pathways regulating RFRP-3 neurons, shedding light on their potential role in reproduction and other processes, and pharmacological studies have probed the target sites of RFRP-3 action. Despite this, there is currently no major consensus on RFRP-3's specific endogenous role(s) in reproductive physiology. Here, we discuss the latest evidence relating to RFRP-3 neuron regulation and function during development and sexual maturation, focusing on rodents. We highlight significant changes in RFRP-3 and Rfrp expression, as well as RFRP-3 neuronal activation, during key stages of postnatal and pubertal development and also discuss recent evidence testing the requisite role of RFRP-3 receptors for normal pubertal timing and developmental LH secretion. Interestingly, some findings suggest that endogenous RFRP-3 signaling may not be necessary for the puberty timing, at least in some species, forcing new hypotheses to be generated regarding this peptide's functional significance to sexual maturation and development.

No MeSH data available.


Changes in neural Rfrp expression during postnatal development in mice. (A) Between the day of birth and adulthood, there are significant changes in the expression of certain subtypes of Rfrp neurons (categorized based on their Rfrp expression levels). Low-expressing (LE) Rfrp cells (yellow arrowheads) are the predominate subtype at birth whereas high-expressing (HE) Rfrp cells (red arrows) are first detectable during the 2nd week of postnatal life and remain present through adulthood. (B) Three graphic representations of Rfrp cell number, total Rfrp expression levels in the brain, and Rfrp neuronal activation (measured by c-Fos co-expression) during rodent postnatal development. P = postnatal day. The purple shading represents the approximate ages when puberty occurs.
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Figure 1: Changes in neural Rfrp expression during postnatal development in mice. (A) Between the day of birth and adulthood, there are significant changes in the expression of certain subtypes of Rfrp neurons (categorized based on their Rfrp expression levels). Low-expressing (LE) Rfrp cells (yellow arrowheads) are the predominate subtype at birth whereas high-expressing (HE) Rfrp cells (red arrows) are first detectable during the 2nd week of postnatal life and remain present through adulthood. (B) Three graphic representations of Rfrp cell number, total Rfrp expression levels in the brain, and Rfrp neuronal activation (measured by c-Fos co-expression) during rodent postnatal development. P = postnatal day. The purple shading represents the approximate ages when puberty occurs.

Mentions: Our lab also examined Rfrp expression over development by measuring Rfrp levels in newborn and adult mice by ISH. We found that not only did Rfrp cell number change markedly over postnatal development, but the levels of Rfrp mRNA in each cell was dramatically different between the two ages. At birth, there were numerous Rfrp neurons detected, but in adulthood, the number of detectable neurons expressing Rfrp was notably less (Figure 1). However, the relative amount of Rfrp mRNA per neuron, indicated by the number of silver grains per individual cell cluster, was higher in adults. This dramatic change in Rfrp mRNA levels per cell demonstrated that while Rfrp cell number is decreasing during postnatal development, each Rfrp cell is a producing, on average, more Rfrp mRNA as the animal ages.


Regulation and Function of RFRP-3 (GnIH) Neurons during Postnatal Development.

Poling MC, Kauffman AS - Front Endocrinol (Lausanne) (2015)

Changes in neural Rfrp expression during postnatal development in mice. (A) Between the day of birth and adulthood, there are significant changes in the expression of certain subtypes of Rfrp neurons (categorized based on their Rfrp expression levels). Low-expressing (LE) Rfrp cells (yellow arrowheads) are the predominate subtype at birth whereas high-expressing (HE) Rfrp cells (red arrows) are first detectable during the 2nd week of postnatal life and remain present through adulthood. (B) Three graphic representations of Rfrp cell number, total Rfrp expression levels in the brain, and Rfrp neuronal activation (measured by c-Fos co-expression) during rodent postnatal development. P = postnatal day. The purple shading represents the approximate ages when puberty occurs.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4585233&req=5

Figure 1: Changes in neural Rfrp expression during postnatal development in mice. (A) Between the day of birth and adulthood, there are significant changes in the expression of certain subtypes of Rfrp neurons (categorized based on their Rfrp expression levels). Low-expressing (LE) Rfrp cells (yellow arrowheads) are the predominate subtype at birth whereas high-expressing (HE) Rfrp cells (red arrows) are first detectable during the 2nd week of postnatal life and remain present through adulthood. (B) Three graphic representations of Rfrp cell number, total Rfrp expression levels in the brain, and Rfrp neuronal activation (measured by c-Fos co-expression) during rodent postnatal development. P = postnatal day. The purple shading represents the approximate ages when puberty occurs.
Mentions: Our lab also examined Rfrp expression over development by measuring Rfrp levels in newborn and adult mice by ISH. We found that not only did Rfrp cell number change markedly over postnatal development, but the levels of Rfrp mRNA in each cell was dramatically different between the two ages. At birth, there were numerous Rfrp neurons detected, but in adulthood, the number of detectable neurons expressing Rfrp was notably less (Figure 1). However, the relative amount of Rfrp mRNA per neuron, indicated by the number of silver grains per individual cell cluster, was higher in adults. This dramatic change in Rfrp mRNA levels per cell demonstrated that while Rfrp cell number is decreasing during postnatal development, each Rfrp cell is a producing, on average, more Rfrp mRNA as the animal ages.

Bottom Line: Here, we discuss the latest evidence relating to RFRP-3 neuron regulation and function during development and sexual maturation, focusing on rodents.We highlight significant changes in RFRP-3 and Rfrp expression, as well as RFRP-3 neuronal activation, during key stages of postnatal and pubertal development and also discuss recent evidence testing the requisite role of RFRP-3 receptors for normal pubertal timing and developmental LH secretion.Interestingly, some findings suggest that endogenous RFRP-3 signaling may not be necessary for the puberty timing, at least in some species, forcing new hypotheses to be generated regarding this peptide's functional significance to sexual maturation and development.

View Article: PubMed Central - PubMed

Affiliation: Department of Reproductive Medicine, University of California, San Diego , La Jolla, CA , USA.

ABSTRACT
RFamide-related peptide-3 (RFRP-3) [mammalian ortholog to gonadotropin-inhibiting hormone (GnIH)] potently inhibits gonadotropin secretion in mammals. Studies of RFRP-3 immunoreactivity and Rfrp expression (the gene encoding RFRP-3) in mammalian brains have uncovered several possible pathways regulating RFRP-3 neurons, shedding light on their potential role in reproduction and other processes, and pharmacological studies have probed the target sites of RFRP-3 action. Despite this, there is currently no major consensus on RFRP-3's specific endogenous role(s) in reproductive physiology. Here, we discuss the latest evidence relating to RFRP-3 neuron regulation and function during development and sexual maturation, focusing on rodents. We highlight significant changes in RFRP-3 and Rfrp expression, as well as RFRP-3 neuronal activation, during key stages of postnatal and pubertal development and also discuss recent evidence testing the requisite role of RFRP-3 receptors for normal pubertal timing and developmental LH secretion. Interestingly, some findings suggest that endogenous RFRP-3 signaling may not be necessary for the puberty timing, at least in some species, forcing new hypotheses to be generated regarding this peptide's functional significance to sexual maturation and development.

No MeSH data available.