Effects of Melatonin on Anterior Pituitary Plasticity: A Comparison Between Mammals and Teleosts

Abstract

Melatonin is a key hormone involved in the photoperiodic signaling pathway. In both teleosts and mammals, melatonin produced in the pineal gland at night is released into the blood and cerebrospinal fluid, providing rhythmic information to the whole organism. Melatonin acts via specific receptors, allowing the synchronization of daily and annual physiological rhythms to environmental conditions. The pituitary gland, which produces several hormones involved in a variety of physiological processes such as growth, metabolism, stress and reproduction, is an important target of melatonin. Melatonin modulates pituitary cellular activities, adjusting the synthesis and release of the different pituitary hormones to the functional demands, which changes during the day, seasons and life stages. It is, however, not always clear whether melatonin acts directly or indirectly on the pituitary. Indeed, melatonin also acts both upstream, on brain centers that control the pituitary hormone production and release, as well as downstream, on the tissues targeted by the pituitary hormones, which provide positive and negative feedback to the pituitary gland. In this review, we describe the known pathways through which melatonin modulates anterior pituitary hormonal production, distinguishing indirect effects mediated by brain centers from direct effects on the anterior pituitary. We also highlight similarities and differences between teleosts and mammals, drawing attention to knowledge gaps, and suggesting aims for future research.

Keywords: adenohypophysis; endocrinology; light; melatonin; melatonin receptors; photoperiod; plasticity; seasonal reproduction.

Figure 1

Schematic representation of daily and seasonal fluctuation in plasma melatonin levels.

Figure 2

Schema of the pituitary in mammals and teleosts. The pituitary is composed of two main parts: the neurohypophysis (posterior pituitary) and the adenohypophysis (anterior pituitary). The neurohypophysis is mainly composed of neuron terminals from neuroendocrine cells with cell soma located in the preoptic-hypothalamic region of the brain. The adenohypophysis contains different hormones producing cell types and can be anatomically divided in pars distalis, pars intermedia and, in mammals but not in teleosts, pars tuberalis.

Figure 3

Schematic view of the putative pathways through which melatonin influence pituitary endocrine activity in mammals. Red continuous lines indicate cell types directly targeted from melatonin. Dashed red lines indicate cells influenced by melatonin via yet unidentified interneurons, paracrine signals or MTNR. Note that melatonin might act only on a few of the illustrated pathway, in different species (see text). Black dashed lines indicate all other interactions between brain and pituitary. POA, preoptic area; PT, pars tuberalis; PD, pars distalis; T3, triiodothyronine; RFRP, RFamide-related peptide; KISS, kisspeptin; GnRH, gonadotropin-releasing hormone; CRH, corticotropin-releasing hormone; TSH, thyroid-stimulating hormone; FSH, follicle-stimulating hormone; LH, luteinising hormone; ACTH, adrenocorticotropic hormone; PRL, prolactin; GH, growth hormone.

Figure 4

Schematic view of the putative pathways through which melatonin influence pituitary endocrine activity in teleosts. Red continuous lines indicate cell types directly targeted from melatonin. Dashed red lines indicate cells influenced by melatonin via yet unidentified interneurons, paracrine signals or Mtnr Note that melatonin might act only on a few of the illustrated pathway, in different species (see text). Black dashed lines indicate all other interactions between brain and pituitary. POA, preoptic area; PD, pars distalis; Kiss, kisspeptin; Gnrh, gonadotropin-releasing hormone; Lh, luteinising hormone; Fsh, follicle-stimulating hormone; Sl, somatolactin; Tsh, thyroid-stimulating hormone; PRL, prolactin; GH, growth hormone.

Figure 5

Melatonin-induced retrograde signaling in mammals and teleosts. Thyrotrope and gonadotrope cells are respectively represented as green and red squares (see legend). Question marks (?) indicate putative pathways not yet demonstrated. In mammals, the photic signal perceived from the retina reaches the pineal gland after being processed from different brain centers (including the suprachiasmatic nucleus, SCN) thus regulating the rhythmic release of melatonin at night. Circulating melatonin acts on pars tuberalis (PT) thyrotropes (PT-TSH) via MTRN1A, thus inhibiting PT-TSH release. In spring, when melatonin levels decrease, PT-TSH secretion is stimulated. PT-TSH, guided by tissue specific glycosylation, binds on its receptors on tanycytes located in the third ventricle of the hypothalamus. Here, PT-TSH regulates local deiodinases (Dio2/Dio3) influencing thyroid hormone metabolism by promoting the conversion of T4 into the bioactive T3. T3 in turn activates arcuate nucleus (ARC) kisspeptin (KISS) neurons via a still unknown mechanism. The following increase in gonadotropin releasing hormone (GnRH) release, stimulates gonadotropes activity in the pars distalis (PD). In teleosts the photic signal is directly perceived from photoreceptive structures within the pineal gland, thus regulating the rhythmic release of melatonin at night. Recent studies suggest that melatonin might regulate the release of a retrograde signal from the pituitary also in teleosts. A distinct population of thyrotrope cells (expressing a second Tsh paralogue, tshbb) located near the pituitary stalk, drastically increase tshbb expression under long photoperiod, a similar response to the one occurring in mammalian PT-TSH. Although melatonin receptors have been described in teleost pituitary and found to display daily and seasonal regulation, their presence in this thyrotrope population as well as the inhibition of Tsh synthesis and release in response to melatonin, remain to be demonstrated.