REPRODUCTION REVIEW Thyroid hormones and seasonal reproductive neuroendocrine interactions Nobuhiro Nakao 1 , Hiroko Ono 1 and Takashi Yoshimura 1,2,3 1 Division of Biomodeling, Laboratory of Animal Functional Genomics, 2 Graduate School of Bioagricultural Sciences, Avian Bioscience Research Center and 3 Institute for Advanced Research, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan Correspondence should be addressed to T Yoshimura; Email: takashiy@agr.nagoya-u.ac.jp Abstract Many animals that breed seasonally measure the day length (photoperiod) and use these measurements as predictive information to prepare themselves for annual breeding. For several decades, thyroid hormones have been known to be involved in this biological process; however, their precise roles remain unknown. Recent molecular analyses have revealed that local thyroid hormone activation in the hypothalamus plays a critical role in the regulation of the neuroendocrine axis involved in seasonal reproduction in both birds and mammals. Furthermore, functional genomics analyses have revealed a novel function of the hormone thyrotropin. This hormone plays a key role in signaling day-length changes to the brain and thus triggers seasonal breeding. This review aims to summarize the currently available knowledge on the interactions between elements of the thyroid hormone axis and the neuroendocrine system involved in seasonal reproduction. Reproduction (2008) 136 1–8 Photoperiodism Many animals inhabiting regions in the temperature zone limit their reproductive activity to specific seasons in order to maximize the survival of their offsprings. Species that have a short incubation or gestation period, such as birds and small mammals, produce young during spring and summer; therefore, they are known as long- day breeders. By contrast, species that have a gestation period of about 5 or 6 months, such as sheep, goats, and deer, enter breeding in the autumn; therefore, they are known as short-day breeders. These seasonal breeding animals use the changes occurring in the day length (photoperiod) as a calendar and accordingly regulate many of their physiological and behavioral processes, including reproduction, migration, molting, hibernation, and body weight alterations. In long-day breeders, the increase in the photoperiod during spring stimulates the secretion of the gonadotropin-releasing hormone (GnRH) from the hypothalamus and the subsequent release of gonadotropins (luteinizing hormone (LH) and follicle-stimulating hormone (FSH)) from the pituitary gland. By contrast, the decrease in the photoperiod during autumn stimulates the secretion of these hormones in short-day breeders. This phenomenon is termed as ‘photoperiodism’. Prolactin secretion is also known to be photoperiodically regulated (reviewed by Morgan & Williams 1996). However, its release is not driven by thyroid hormones ( Dahl et al. 1994). Furthermore, previous studies have revealed that the blockade of seasonal reproductive functions due to lesions or hypothalamo-pituitary disconnection does not affect the seasonal secretion of prolactin (Juss 1993, Lincoln 2002). Therefore, we do not focus on prolactin in the present review. Melatonin and seasonality In all vertebrates, melatonin is secreted on a daily basis by the pineal gland under the control of the circadian system; its secretion peaks during the subjective night and ceases during the day. The duration of melatonin secretion tracks night length and in mammal this humoral signal is considered a crucial component of the mechanism governing mammalian photoperiodism (Reiter 1993, Goldman 2001). In mammals, light signals are received by the eye and are then transmitted to the circadian pacemaker in the hypothalamus, i.e., the suprachiasmatic nucleus (SCN). The SCN drives the nocturnal rhythm of melatonin secretion by the pineal gland, and a lesion in the SCN abolishes the circadian rhythms that govern the production and secretion of this hormone (Scott et al. 1995, Tessonneaud et al. 1995). Hamsters and sheep have been shown to develop photoperiodic blindness following pinealectomy (Hoffman & Reiter 1965, Bittman et al. 1983). In addition, q 2008 Society for Reproduction and Fertility DOI: 10.1530/REP-08-0041 ISSN 1470–1626 (paper) 1741–7899 (online) Online version via www.reproduction-online.org