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

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.

Prior aerobic physical training modulates neuropeptide expression and central thermoregulation after ovariectomy in the rat.

This study compared the effects of aerobic physical training and estradiol (E2) replacement on central pathways involved with thermoregulation in ovariectomized rats. Rats were assigned to untrained ovariectomized treated with placebo (UN-OVX), untrained ovariectomized treated with E2 (E2-OVX), and trained ovariectomized (TR-OVX) groups. Tail skin temperature (TST), internal temperature (Tint), and basal oxygen consumption (VO2) were recorded. Neuronal activity, brain expression of Kiss1, NKB and Prodyn, and central norepinephrine (NE) levels were measured. UN-OVX had the highest TST. Compared to UN-OVX rats, TR-OVX and E2-OVX had lower Fos expression in the paraventricular and arcuate (ARC) nuclei, and lower double labeling for Tyrosine Hydroxylase and Fos in the brainstem. Compared to UN-OVX, only TR-OVX group exhibited lower kisspeptin (Kiss1), neurokinin B (NKB), and prodynorphin expression in the ARC and higher central NE levels. Aerobic physical training before menopause may prevent the heat dissipation imbalance induced by reduction of E2, through central NE release, modulation of Kiss1, NKB and prodynorphin expression in neurons from ARC nucleus.

Kisspeptin Treatment Restores Ovarian Function in Rats with Hypothyroidism.

Background: Hypothyroidism causes ovarian dysfunction and infertility in women, in addition to being associated with hyperprolactinemia and reduced hypothalamic expression of kisspeptin (Kp). However, it remains unknown whether and how Kp is able to reverse the ovarian dysfunction caused by hypothyroidism. Methods: Hypothyroidism was induced in adult female Wistar rats using 6-propyl-2-thiouracil for 3 months. In the last month, half of the animals received Kp10. Blood samples were collected for dosage of free thyroxine, thyrotropin (TSH), luteinizing hormone (LH), prolactin (PRL), progesterone (P4), and estradiol (E2), and uteruses and ovaries were collected for histomorphometry. Body and ovarian weight and the number of corpora lutea were also evaluated. Half of the brains were evaluated by immunohistochemistry to Kp, and the other half had the arcuate nucleus of hypothalamus (ARC) and preoptic area microdissected for gene evaluation of Kiss1, Nkb, Pdyn, and Gnrh1. The pituitary gland and corpora lutea were also dissected for gene evaluation. Results: Hypothyroidism kept the animals predominantly acyclic and promoted a reduction in ovarian weight, number of corpora lutea, endometrial thickness, number of endometrial glands, and plasma LH, in addition to increasing the luteal messenger RNA (mRNA) expression of Star and Cyp11a1 and reducing 20αHsd. An increase in plasma PRL and P4 levels was also caused by hypothyroidism. Kp immunoreactivity and Kiss1 and Nkb mRNA levels in the ARC and Kiss1 in the anteroventral periventricular nucleus of hypothalamus were reduced in hypothyroid rats. Hypothyroid animals had lower pituitary gene expression of Gnrhr, Lhb, Prl, and Drd2, and an increase in Tshb. The treatment with Kp10 restored estrous cyclicality, plasma LH, ovarian and uterine morphology, and Cyp11a1, 3ßHsd, and 20αHsd mRNA levels in the corpora lutea. Kp10 treatment did not alter gene expression for Kiss1 or Nkb in the ARC of hypothyroid rats. Nevertheless, Kp10 increased Lhb mRNA levels and reduced Tshb in the pituitary compared with the hypothyroid group. Conclusions: The present findings characterize the inhibitory effects of hypothyroidism on the hypothalamic-pituitary-gonadal axis in female rats and demonstrate that Kp10 is able to reverse the ovarian dysfunction caused by hypothyroidism, regardless of hyperprolactinemia.