Universality and diversity in the signal transduction pathway that regulates seasonal reproduction in vertebrates

Abstract

Most vertebrates living outside the tropical zone show robust physiological responses in response to seasonal changes in photoperiod, such as seasonal reproduction, molt, and migration. The highly sophisticated photoperiodic mechanism in Japanese quail has been used to uncover the mechanism of seasonal reproduction. Molecular analysis of quail mediobasal hypothalamus (MBH) revealed that local thyroid hormone activation within the MBH plays a critical role in the photoperiodic response of gonads. This activation is accomplished by two gene switches: thyroid hormone-activating (DIO2) and thyroid hormone-inactivating enzymes (DIO3). Functional genomics studies have shown that long-day induced thyroid-stimulating hormone (TSH) in the pars tuberalis (PT) of the pituitary gland regulates DIO2/3 switching. In birds, light information received directly by deep brain photoreceptors regulates PT TSH. Recent studies demonstrated that Opsin 5-positive cerebrospinal fluid (CSF)-contacting neurons are deep brain photoreceptors that regulate avian seasonal reproduction. Although the involvement of TSH and DIO2/3 in seasonal reproduction has been confirmed in various mammals, the light input pathway that regulates PT TSH in mammals differs from that of birds. In mammals, the eye is the only photoreceptor organ and light information received by the eye is transmitted to the pineal gland through the circadian pacemaker, the suprachiasmatic nucleus. Nocturnal melatonin secretion from the pineal gland indicates the length of night and regulates the PT TSH. In fish, the regulatory machinery for seasonal reproduction, from light input to neuroendocrine output, has been recently demonstrated in the coronet cells of the saccus vasculosus (SV). The SV is unique to fish and coronet cells are CSF-contacting neurons. Here, we discuss the universality and diversity of signal transduction pathways that regulate vertebrate seasonal reproduction.

Keywords: cerebrospinal fluid-contacting neuron; circadian rhythm; coronet cell; deep brain photoreceptor; pars tuberalis; saccus vasculosus; thyroid hormone; thyroid-stimulating hormone.

Figure 1

Signal transduction pathway regulating seasonal reproduction in birds. Light information received by deep brain photoreceptors is transmitted to the pars tuberalis (PT) of the pituitary gland, a regulatory hub for seasonal reproduction. Long day-induced thyrotropin (TSH) in the PT acts on ependymal cells to induce a thyroid hormone-activating enzyme, DIO2. The bioactive thyroid hormone, T₃ is converted by DIO2 from the prohormone, T₄. T₃ regulates seasonal morphological changes in GnRH nerve terminals and glial processes, thereby regulating or modulating GnRH secretion.

Figure 2

Family of cerebrospinal fluid (CSF)-contacting neurons. (A) Schematic drawings and picture of OPN5 positive CSF-contacting neurons in the paraventricular organ (PVO) of quail. (B) Schematic drawing and picture of coronet cells in the salmon saccus vasculosus (SV). The SV consists of coronet cells (C) and supporting cells (S). Globules of coronet cells are based on 9 × 2 + 0 cilia. (C) Schematic drawing and picture of a mammalian retina and photoreceptor. The outer segments of rod and cone cells are also based on 9 × 2 + 0 cilia. ^*third ventrile. RPE, retinal pigment epithelium, OS, outer segment, IS, inner segment, ONL, outer nuclear layer, INL inner nuclear layer, GCL, ganglion cell layer. Scale bars indicate 20 μm.

Figure 3

Universality and diversity of signal transduction pathways that regulate seasonal reproduction in vertebrates. (A) Eyes are the only photoreceptor organ in mammals. Light information is transmitted through the suprachiasmatic nucleus (SCN) to the pineal gland. Photoperiodic information is encoded by the pattern of melatonin secretion from the pineal gland. Melatonin regulates the “springtime hormone,” TSH, in the pars tuberalis (PT) of the pituitary gland. (B) In contrast to mammals, light information is directly received by deep brain photoreceptors in birds and is then transmitted to the PT to induce TSH. (C) In fish, all of the machinery required for seasonal reproduction (from photoreceptors to neuroendocrine output) is located in the saccus vasculosus (SV).