Intracerebroventricular injection of RFRP-3 delays puberty onset and stimulates growth hormone secretion in female rats

Han, Xiao; He, Yuanyuan; Zeng, Guo; Wang, Yonghong; Sun, Wen; Liu, Junchao; Sun, Yun; Yu, Jian

doi:10.1186/s12958-017-0254-5

Cited by 35 publications

(32 citation statements)

References 48 publications

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“…Delayed puberty in our study, may be due to increased Rfrp expression. Similarly, in a study by Han et al (26) it was shown that intracerebroventricular injection of RFRP-3 between days 28 and 36, at the time of puberty onset, delayed vaginal opening in rats. Furthermore, Rfrp expression in DMN decreased during early pre-pubertal stages in the mouse.…”

Section: Discussionmentioning

confidence: 69%

Maternal Aromatase Inhibition Effects on RFamide-Related Peptide-3 and Gonadotropin Releasing Hormone in Adult Murine Offspring With Polycystic Ovary Syndrome

Shaaban¹,

Tamadon²,

Shirazi³

et al. 2020

Preprint

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Background: Despite the prevalence of polycystic ovary syndrome (PCOS) among childbearing women and the development of many animal models for this syndrome, information on its etiology is still scarce. Intrauterine hyperandrogenic environment may underlie changes at the levels of hypothalamus, pituitary and ovary organization in female offspring, and PCOS later in life. Letrozole, has been shown to mimic reproductive and metabolic characteristics of PCOS in adult rodent models. Therefore, the aim of this research was to assess the condition in a prenatal letrozole-treated rat model. Methods: Twenty-eight female rats from dams receiving letrozole at certain doses during late pregnancy were used in the trial. Pregnant Sprague-Dawley rats (n=21) received letrozole treatment on days 16-18 gestation at doses 1.25, 1.0, 0.75, 0.5, and 0.25 mg/kg body weight (BW).Results: Prenatal letrozole-treatment delayed parturition time and reduced the litter size in pregnant dams (P<0.0001). Late puberty onset, irregular ovarian cyclicity, increased anogenital distance (AGD), body weight gain, and serum testosterone concentration and reduced estradiol levels (P<0.0001) were observed in the female offspring of dams receiving 1.25 and 1 mg/kg BW letrozole. Furthermore, Letrozole at 1.25 and 1 mg/kg BW showed increased Rfrp and decreased Gnrh mRNA expression (P<0.0001). Conclusions: Letrozole treatment at doses 1 mg/kg BW and lower was not feto-toxic. It was concluded that 1 mg/kg BW letrozole may be suggested for prenatal PCOS induction.

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Section: Discussionmentioning

confidence: 69%

Maternal Aromatase Inhibition Effects on RFamide-Related Peptide-3 and Gonadotropin Releasing Hormone in Adult Murine Offspring With Polycystic Ovary Syndrome

Shaaban¹,

Tamadon²,

Shirazi³

et al. 2020

Preprint

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“…On the other hand, GPR147 mRNA expression in female rats increases from P16, peaks at P28, and decreases from P35 . Central administration of GnIH (RFRP3) from P28 to P36 twice a day significantly decreases serum LH and estradiol concentration, delay uterine maturation and vaginal opening in female rats . These results suggest that decreases in GnIH and/or GPR147 may also facilitate puberty in male and female rats.…”

Section: Regulation Of Pubertymentioning

confidence: 89%

Reproductive neuroendocrinology of mammalian gonadotropin‐inhibitory hormone

Ubuka

Tsutsui

2019

Reprod Medicine & Biology

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Background Gonadotropin‐inhibitory hormone (GnIH) was discovered in the Japanese quail brain in 2000 as a hypothalamic neuropeptide that suppresses luteinizing hormone release from cultured quail anterior pituitary. Methods The authors investigated the existence of mammalian orthologous peptides to GnIH and their physiological functions in the following 19 years of research. Main findings Mammals have orthologous peptide to GnIH, often described RFamide‐related peptide, expressed in the hypothalamus and gonads. Mammalian GnIH may also suppress gonadotropin synthesis and release by suppressing gonadotropin‐releasing hormone (GnRH) synthesis and release in addition to directly suppressing gonadotropin synthesis and release from the pituitary. Mammalian GnIH may also suppress kisspeptin, a stimulator of GnRH, release. Mammalian GnIH is also expressed in the testis and ovary and suppresses gametogenesis and sex steroid production acting in an autocrine/paracrine manner. Thus, mammalian GnIH may act at all levels of the hypothalamic‐pituitary‐gonadal axis to suppress reproduction. GnIH may be involved in the regulation of puberty, estrous or menstrual cycle, seasonal reproduction, and stress responses. Conclusion Studies suggest that mammalian GnIH is an important neuroendocrine suppressor of reproduction in mammals.

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“…To evaluate the hypothalamic expressions of Lin28a and Lin28b mRNA and let7a and let7b miRNA, hypothalamic samples were collected and stored at −80°C. The uteruses and ovaries were immediately dissected out of the surrounding fat by opening the abdominal cavity and were weighed to evaluate the organ coefficients according to the organ index formula ([organ wet weight (g)/body weight (g)] × 10 −4 ) [ 49 ].…”

Section: Methodsmentioning

confidence: 99%

Precocious Puberty and the Lin28/Let7 Pathway: The Therapeutic Effect of the Nourishing “Yin” and Purging “Fire” Traditional Chinese Medicine Mixture in a Rat Model

Han

Sun

et al. 2018

Evidence-Based Complementary and Alternative Medicine

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The present study aims to investigate the effects of the nourishing “Yin” and purging “Fire” Traditional Chinese Medicine (TCM) herb mixture on precocious puberty and TCM may act through hypothalamic Lin28/let7 pathway expression in the precocious puberty model rats. Meanwhile, to confirm the relationship between Lin28/let7 pathway and puberty by overexpression Lin28a, in the first part of this study, female rats were randomly allocated into untreated controls, the precocious puberty (PP) model group, the PP control group, and the PP + TCM group. Rats on postnatal day 5 were injected danazol to establish the PP model. From days 15 to 35, the rats in the TCM group were given the TCM twice daily. Vaginal opening, sex-related hormones, and body and reproductive organ weights were measured, and the expressions of hypothalamic Lin28a and Lin28b mRNA and let7a and let7b miRNA were detected. In addition, in the second part, the effects of overexpression of Lin28a on the vaginal opening time were evaluated. In the two parts of the study, we found that, at the onset of puberty, a decrease in ovary weight, an increase in the serum levels of luteinizing hormone and progesterone, and increased expression levels of hypothalamic Lin28b mRNA were observed in the PP + TCM group compared to the PP model group. The vaginal opening time was significantly delayed upon overexpression of Lin28a. Above all, the mechanism by which the TCM treats precocious puberty is thus likely to be associated with inhibition of the hypothalamic Lin28/let7 signaling pathway and our findings provide in-depth insight into the relationship between the overexpression of Lin28a gene in the hypothalamus and the onset of puberty.

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Intracerebroventricular injection of RFRP-3 delays puberty onset and stimulates growth hormone secretion in female rats

Cited by 35 publications

References 48 publications

Maternal Aromatase Inhibition Effects on RFamide-Related Peptide-3 and Gonadotropin Releasing Hormone in Adult Murine Offspring With Polycystic Ovary Syndrome

Maternal Aromatase Inhibition Effects on RFamide-Related Peptide-3 and Gonadotropin Releasing Hormone in Adult Murine Offspring With Polycystic Ovary Syndrome

Reproductive neuroendocrinology of mammalian gonadotropin‐inhibitory hormone

Precocious Puberty and the Lin28/Let7 Pathway: The Therapeutic Effect of the Nourishing “Yin” and Purging “Fire” Traditional Chinese Medicine Mixture in a Rat Model

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