Leptin stimulates pituitary prolactin release through an extracellular signal-regulated kinase-dependent pathway

Abstract

Leptin was initially identified as a regulator of appetite and weight control centers in the hypothalamus, but appears to be involved in a number of physiological processes. This study was carried out to examine the possible role of leptin in regulating prolactin (PRL) release using the teleost pituitary model system. This advantageous system allows isolation of a nearly pure population of lactotropes in their natural, in situ aggregated state. The rostral pars distalis were dissected from tilapia pituitaries and exposed to varying concentrations of leptin (0, 1, 10, 100 nM) for 1 h. Release of PRL was stimulated by leptin in a potent and concentration-dependent manner. A time-course experiment showed that the strongest response in PRL release with leptin occurs within the first hour (approximately sixfold), and stimulation was sustained after 16 h (approximately twofold). Many of the actions of leptin are mediated by the activation of extracellular signalregulated kinase (ERK1/2) but nothing is known about the cellular mechanisms by which leptin might regulate PRL secretion in vertebrates. We therefore tested whether ERK1/2 might be involved in the leptin PRL response and found that the ERK inhibitor, PD98059, hindered leptininduced PRL release. We further analyzed leptin response by quantifying tyrosine and threonine phosphorylation of ERK1/2 using western blots. One hour incubation with leptin induced a concentration-dependent increase in phosphorylated, and thus active, ERK1/2. Our data show that leptin is a powerful stimulator of in vitro PRL release and that its actions occur in part through stimulation of ERK1/2.

Role for leptin in promoting glucose mobilization during acute hyperosmotic stress in teleost fishes

“…Commercially prepared rhLep is commonly used for comparative studies in teleosts (Tipsmark et al 2008, Won et al 2012. In particular, in vivo administration of rhLep has been shown to decrease appetite in fishes, a classic effect of leptin in mammals (Ahima & Flier 2000, Won et al 2012.…”

Seasonal effects of central leptin infusion on secretion of melatonin and prolactin and on SOCS-3 gene expression in ewes

“…This observation is consonant with observations of Accorsi et al (2007) who noted a leptin-mediated enhancement of PRL release in bovine adenohypophyseal explants in culture, although Nonaka et al (2007) reported little effect of leptin on PRL release from primary cultures of porcine anterior pituitary cells. Interestingly, Tipsmark et al (2008) have shown that leptin is a very potent PRL secretagogue in teleost pituitary cultures. Secretion of PRL is tightly connected to melatonin release by the pineal gland, which is a key step in integrating the annual change in day length.…”

Evolution of Leptin Structure and Function

“…Lep mRNA is expressed at lower levels in heart, placenta and fetal tissues [93,94], the pituitary gland, where leptin may modulate pituitary hormone secretion [95,96,97], and in the brain [98] where the hormone can influence neural development [36,99,100] and cognitive function in the adult [101]. In nonmammalian species, Lep mRNA appears to be more widely expressed compared with mammals, although the major sites of expression may differ among taxa [30].…”