Kisspeptin Treatment Restores Ovarian Function in Rats with Hypothyroidism

Oliveira, Lisa; Silva, Thayna Queiroz Menezes da; Barbosa, Erikles Macêdo; Cordeiro, Jeane Martinha dos Anjos; Santos, Luciano Cardoso; Henriques, Patricia C; Santos, Bianca Reis; Gusmao, Daniela O.; Macedo, Isabella Oliveira de; Szawka, Raphael E.; Silva, Juneo Freitas

doi:10.1089/thy.2021.0638

Cited by 8 publications

(10 citation statements)

References 61 publications

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“…Although the PRL values in the present study are low, other studies with male rats have shown discrepancy in the range of PRL levels 64 – 69 , which may be the result of different ELISA protocols and, mainly, different models of hyperprolactinemia (for example: induction by administration of ovine PRL, cabergoline, haloperidol and others, in addition to surgical methods). Notably, the effect of Kp10 on PRL concentration observed here in the male was different from that recently described in hypothyroid female 20 , in which Kp10 increased plasma LH and restored ovarian cyclicity without altering the hyperprolactinemia 20 . This suggests that there are differences in the PRL modulation by kisspeptin between male and female rats in the hypothyroid condition.…”

Section: Discussioncontrasting

confidence: 99%

“…In the present study, hypothyroidism also reduced Drd2 gene expression in the pituitary, likewise in hypothyroid female rats 20 . This suggests another mechanism through which hypothyroidism can cause hyperprolactinemia in addition to the recognized stimulatory effect of the increased TRH on PRL secretion during hypothyroidism 71 .…”

Section: Discussionsupporting

confidence: 73%

“…In this region, kisspeptin neurons co-express neurokinin-B (NKB) and dynorphin (KNDy neurons), which exert stimulatory and inhibitory effects on kisspeptin release, respectively, resulting in a pulsatile drive to the GnRH secretion 18 , 19 . We recently demonstrated that hypothyroidism in female rats reduces kisspeptin and Nkb expression in KNDy neurons, and the treatment with kisspeptin-10 (Kp10) restores ovarian cyclicity and plasma LH levels in these animals 20 . However, there is still little knowledge about alterations in KNDy neuronal function in male rats with hypothyroidism.…”

Section: Introductionmentioning

confidence: 99%

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Kisspeptin treatment reverses high prolactin levels and improves gonadal function in hypothyroid male rats

Santos,

dos Anjos Cordeiro,

da Silva Santana

et al. 2023

Sci Rep

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We evaluated whether the administration of kisspeptin-10 (Kp10) is capable of restoring gonadal function in hypothyroid male rats. Hypothyroidism was induced with 6-propyl-2-thiouracil (PTU) for three months. In the last month, half of the hypothyroid animals were treated with Kp10. Hypothyroidism reduced testicular and sex gland mass, decreased the proliferation of the seminiferous epithelium, and compromised sperm morphology, motility, and vigor. A decrease in plasma LH and testosterone levels and an increase in prolactin secretion were observed in the hypothyroid rats. Hypothyroidism reduced Kiss1 and Kiss1r protein and gene expression and Star and Cyp11a1 mRNA levels in the testis. Furthermore, it reduced Lhb, Prl, and Drd2 and increased Tshb and Gnrhr expression in the pituitary. In the hypothalamus, hypothyroidism increased Pdyn and Kiss1r while reducing Gnrh1. Kp10 treatment in hypothyroid rats restored testicular and seminal vesicle morphology, improved sperm morphology and motility, reversed high prolactin levels, and increased LH and testosterone levels. In addition, Kp10 increased testicular expression of Kiss1, Kiss1r, Fshr, and Nr5a1 and pituitary Kiss1 expression. Our findings describe the inhibitory effects of hypothyroidism on the male gonadal axis and sperm quality and demonstrate that Kp10 treatment reverses high prolactin levels and improves gonadal function and sperm quality in hypothyroid rats.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 73%

Section: Introductionmentioning

confidence: 99%

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Kisspeptin treatment reverses high prolactin levels and improves gonadal function in hypothyroid male rats

Santos,

dos Anjos Cordeiro,

da Silva Santana

et al. 2023

Sci Rep

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“…Although T4 replacement is the first choice in patients with hypothyroidism, some patients are refractory to T4 replacement ( 41 ) and need other therapeutic alternatives when they need to treat a medical condition, such as infertility problems. In this sense, exogenous kisspeptin has been shown to restore ovarian function in hypothyroid rats ( 42 ). Furthermore, studies have shown that kisspeptin administration has an immunomodulatory effect on gestation ( 15 ) and an antioxidative effect on the ovary ( 43 ), liver ( 44 ), and testicle ( 45 ), and blocks the occurrence of reticular stress in hypothalamic GT1-7 cell line ( 46 ).…”

Section: Introductionmentioning

confidence: 99%

Kisspeptin treatment improves fetal-placental development and blocks placental oxidative damage caused by maternal hypothyroidism in an experimental rat model

et al. 2022

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Maternal hypothyroidism is associated with fetal growth restriction, placental dysfunction, and reduced kisspeptin/Kiss1R at the maternal-fetal interface. Kisspeptin affects trophoblastic migration and has antioxidant and immunomodulatory activities. This study aimed to evaluate the therapeutic potential of kisspeptin in the fetal-placental dysfunction of hypothyroid Wistar rats. Hypothyroidism was induced by daily administration of propylthiouracil. Kisspeptin-10 (Kp-10) treatment was performed every other day or daily beginning on day 8 of gestation. Feto-placental development, placental histomorphometry, and expression levels of growth factors (VEGF, PLGF, IGF1, IGF2, and GLUT1), hormonal (Dio2) and inflammatory mediators (TNFα, IL10, and IL6), markers of hypoxia (HIF1α) and oxidative damage (8-OHdG), antioxidant enzymes (SOD1, Cat, and GPx1), and endoplasmic reticulum stress mediators (ATF4, GRP78, and CHOP) were evaluated on day 18 of gestation. Daily treatment with Kp-10 increased free T3 and T4 levels and improved fetal weight. Both treatments reestablished the glycogen cell population in the junctional zone. Daily treatment with Kp-10 increased the gene expression levels of Plgf, Igf1, and Glut1 in the placenta of hypothyroid animals, in addition to blocking the increase in 8-OHdG and increasing protein and/or mRNA expression levels of SOD1, Cat, and GPx1. Daily treatment with Kp-10 did not alter the higher protein expression levels of VEGF, HIF1α, IL10, GRP78, and CHOP caused by hypothyroidism in the junctional zone compared to control, nor the lower expression of Dio2 caused by hypothyroidism. However, in the labyrinth zone, this treatment restored the expression of VEGF and IL10 and reduced the GRP78 and CHOP immunostaining. These findings demonstrate that daily treatment with Kp-10 improves fetal development and placental morphology in hypothyroid rats, blocks placental oxidative damage, and increases the expression of growth factors and antioxidant enzymes in the placenta.

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“…Thyroid dysfunction affects the reproductive function, causing menstrual irregularities, polycystic ovaries in women, and abnormalities in testicular cell proliferation and differentiation, changes in testicular size, functional and hormonal changes in the male reproductive system [24,25,26].…”

Section: Discussionmentioning

confidence: 99%

Disorders in connections of the hypothalamic-pituitarygonadal axis in rats with Guerin’s carcinoma against the background of induced hypothyroidism

Бандовкина¹,

Frantsiyants²,

Kaplieva³

et al. 2023

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Aims: to study the content of regulatory peptides in the hypothalamus and pituitary gland, as well as sex steroids in the gonads in rats of both sexes with Guerin’s carcinoma against the background of hypothyroidism. Materials and methods. Our experiment was performed in white outbred rats of both sexes with induced hypothyroidism, against the background of which Guerin’s carcinoma was transplanted. In 1% homogenates of the pituitary and the hypothalamus and in 10% homogenates of the gonads in the animals from the main and reference groups, the levels of GnRH (Casabio, China) were determined by the ELISA method using standard kits, and the content of LH, FSH, estradiol (E2), testosterone (T) and progesterone (P4) by the RIA method (Immunotech, Czech Republic). Statistical analysis of the results was performed using the Statistica 10.0 software package. Results. In females of the main group, the level of GnRH in the hypothalamus increased by 1.6 times, but the content of LH and FSH in the pituitary gland decreased, while in males the content of GnRH decreased by 1.4 times and FSH by 1.6 times compared with the intact animals. In the gonads of females of the main group, the content of E2 and T decreased by 1.3 times, but the level of P4 increased by 4.7 times, while in males the T production decreased by 7.1 times. Hypothyroidism, against the background of which Guerin’s carcinoma developed, had a significant effect both on the central links of the HPG axis and the peripheral ones, producing an additional hormonal imbalance in sex steroids

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Kisspeptin Treatment Restores Ovarian Function in Rats with Hypothyroidism

Cited by 8 publications

References 61 publications

Kisspeptin treatment reverses high prolactin levels and improves gonadal function in hypothyroid male rats

Kisspeptin treatment reverses high prolactin levels and improves gonadal function in hypothyroid male rats

Kisspeptin treatment improves fetal-placental development and blocks placental oxidative damage caused by maternal hypothyroidism in an experimental rat model

Disorders in connections of the hypothalamic-pituitarygonadal axis in rats with Guerin’s carcinoma against the background of induced hypothyroidism

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