{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:32:34Z","timestamp":1789173154578,"version":"build-2803163510"},"reference-count":59,"publisher":"SAGE Publications","issue":"12","license":[{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Thyroid\u00ae"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      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 (P\n                      <jats:sub>4<\/jats:sub>\n                      ), and estradiol (E\n                      <jats:sub>2<\/jats:sub>\n                      ), 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:italic toggle=\"yes\">Star<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">Cyp11a1<\/jats:italic>\n                      and reducing\n                      <jats:italic toggle=\"yes\">20\u03b1Hsd<\/jats:italic>\n                      . An increase in plasma PRL and P\n                      <jats:sub>4<\/jats:sub>\n                      levels was also caused by hypothyroidism. Kp immunoreactivity and\n                      <jats:italic toggle=\"yes\">Kiss1<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">Nkb<\/jats:italic>\n                      mRNA levels in the ARC and\n                      <jats:italic toggle=\"yes\">Kiss1<\/jats:italic>\n                      in the anteroventral periventricular nucleus of hypothalamus were reduced in hypothyroid rats. Hypothyroid animals had lower pituitary gene expression of\n                      <jats:italic toggle=\"yes\">Gnrhr<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Lhb<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Prl<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">Drd2<\/jats:italic>\n                      , and an increase in\n                      <jats:italic toggle=\"yes\">Tshb<\/jats:italic>\n                      . The treatment with Kp10 restored estrous cyclicality, plasma LH, ovarian and uterine morphology, and\n                      <jats:italic toggle=\"yes\">Cyp11a1<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">3\u03b2Hsd<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">20\u03b1Hsd<\/jats:italic>\n                      mRNA levels in the corpora lutea. Kp10 treatment did not alter gene expression for\n                      <jats:italic toggle=\"yes\">Kiss1<\/jats:italic>\n                      or\n                      <jats:italic toggle=\"yes\">Nkb<\/jats:italic>\n                      in the ARC of hypothyroid rats. Nevertheless, Kp10 increased\n                      <jats:italic toggle=\"yes\">Lhb<\/jats:italic>\n                      mRNA levels and reduced\n                      <jats:italic toggle=\"yes\">Tshb<\/jats:italic>\n                      in the pituitary compared with the hypothyroid group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>The present findings characterize the inhibitory effects of hypothyroidism on the hypothalamic\u2013pituitary\u2013gonadal axis in female rats and demonstrate that Kp10 is able to reverse the ovarian dysfunction caused by hypothyroidism, regardless of hyperprolactinemia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/thy.2021.0638","type":"journal-article","created":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T03:46:36Z","timestamp":1656474396000},"page":"1568-1579","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":13,"title":["Kisspeptin Treatment Restores Ovarian Function in Rats with Hypothyroidism"],"prefix":"10.1177","volume":"32","author":[{"given":"Luciana Santos","family":"de Oliveira","sequence":"first","affiliation":[{"name":"Centro de Microscopia Eletronica, Departamento de Ciencias Biologicas, Universidade Estadual de Santa Cruz, Ilheus, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thayna Queiroz Menezes","family":"da Silva","sequence":"additional","affiliation":[{"name":"Centro de Microscopia Eletronica, Departamento de Ciencias Biologicas, Universidade Estadual de Santa Cruz, Ilheus, 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Costa","family":"Henriques","sequence":"additional","affiliation":[{"name":"Departamento de Fisiologia e Biof\u00edsica, Instituto de Ciencias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca Reis","family":"Santos","sequence":"additional","affiliation":[{"name":"Centro de Microscopia Eletronica, Departamento de Ciencias Biologicas, Universidade Estadual de Santa Cruz, Ilheus, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela de Oliveira","family":"Gusmao","sequence":"additional","affiliation":[{"name":"Departamento de Fisiologia e Biof\u00edsica, Instituto de Ciencias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella Oliveira","family":"de Macedo","sequence":"additional","affiliation":[{"name":"Centro de Microscopia Eletronica, Departamento de Ciencias 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