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Delivery of Ovarian Hormones for Bone Health
Published in Emmanuel Opara, Controlled Drug Delivery Systems, 2020
The ovaries are part of the complex HPO axis (Figure 7.1). This system operates through the secretion of GnRH from the hypothalamus to the anterior pituitary via the hypophyseal portal system of the infundibulum,2 as triggered by upstream signals such as kisspeptin cells in the diencephalon.90 GnRH, in turn, leads to secretion of FSH and LH from the anterior pituitaries, which enter the bloodstream to reach the ovaries, where they promote secretion of estrogen, progesterone, and other hormones. The secretion of estrogen and progesterone as well as hormones, including activin, inhibin, and testosterone, from the ovaries have feedforward and feedback control mechanisms on the secretion of the hypothalamic and pituitary hormones. As such, loss of the ovarian hormones due to loss of ovarian function has systemic effects not only on target tissues, to be discussed below, but also on the hormone levels of the hypothalamic and pituitary hormones. That is, the loss or change in ovarian hormone production (e.g., estrogen and inhibin) and blood concentrations also leads to changes in plasma concentrations of the anterior pituitary hormones before, during, and after menopause.104,123 Although changes in the ovarian hormone levels affect hypothalamus and pituitary hormones, the converse is also true. Indeed, changes in plasma levels of FSH and changes in LH and GnRH are observed prior to decreases in estrogen and progesterone concentrations associated with the menopausal transition.146
Effects of 17α-ethinylestradiol on the neuroendocrine gonadotropic system and behavior of European sea bass larvae (Dicentrarchus labrax)
Published in Journal of Toxicology and Environmental Health, Part A, 2023
S Soloperto, S Olivier, A Poret, C Minier, MP Halm-Lemeille, C Jozet-Alves, S Aroua
Kisspeptins are considered to be essential regulators of the HPG axis in vertebrates, responding directly to estrogenic stimuli. While this process is well documented in mammals, different situations were found in teleost fish, with species possessing either one or two kiss genes (Pasquier et al. 2014). In sea bass, two genes were identified (Felip et al. 2009) and in the present study, both kiss1 and kiss2 gene expression were measured. First, both genes were shown to be expressed during larval development. In addition, upregulation of kiss1 expression was detected after EE2 exposure while kiss2 expression was not modified (observed in experiment 1 and 2 Supplementary data I-b, with minor inconsistencies that might be attributed to interindividual variance). This action of EE2 on kiss gene expression may be related to the presence of nuclear estrogen receptors (ER). Indeed, in the brain of adult sea bass, Escobar et al. (2013) demonstrated by using double in situ hybridization that kiss1-expressing neurons located in the mediobasal hypothalamus co-express esr1 and esr2a. In contrast, no co-expression with ER was observed in kiss1 neurons of the habenula, nor in the kiss2 neurons. Data suggest a potential direct action of estrogens on kiss1 regulation, which is in accordance with our findings. Further, upregulation of kiss1 was previously reported in fish species such as medaka and zebrafish after exposure to estrogens (Mitani et al. 2010; Servili et al. 2011) or xenoestrogens (Faheem et al. 2019; Thayil et al. 2020), and recently in sea bass eleutheroembryos (Soloperto et al. 2022a). Regarding kiss2-expressing cells, estrogens do not seem to directly regulate kiss2 expression in the adult sea bass as cells do not express ER (Escobar et al. 2013) and as no variation in kiss2 expression was observed after gonadectomy and estradiol replacement (Alvarado et al., 2016). Our current results in sea bass larvae, like those obtained previously in eleutheroembryos (Soloperto et al., 2022a), confirm that an exposure to XEs does not apparently affect kiss2 expression in sea bass. Nevertheless, this is not the case in all fish species, as kiss2 expression was stimulated in juvenile zebrafish or sturgeon after estradiol treatment (Servili et al. 2011; Yue et al. 2019).