The subfornical organ: A novel site for prolactin action

Abstract

Prolactin (PRL) is a peptide hormone that performs over 300 biological functions, including those that require binding to prolactin receptor (PRL-R) in neurones within the central nervous system (CNS). To enter the CNS, circulating PRL must overcome the blood-brain barrier. Accordingly, areas of the brain that do not possess a blood-brain barrier, such as the subfornical organ (SFO), are optimally positioned to interact with systemic PRL. The SFO has been classically implicated in energy and fluid homeostasis but has the potential to influence oestrous cyclicity and gonadotrophin release, which are also functions of PRL. We aimed to confirm and characterise the expression of PRL-R in the SFO, as well as identify the effects of PRL application on membrane excitability of dissociated SFO neurones. Using a quantitative real-time polymerase chain reaction, we found that PRL-R mRNA in the SFO of male and female Sprague Dawley rats did not significantly differ between juvenile and sexually mature rats (P = .34), male and female rats (P = .97) or across the oestrous cycle (P = .54). Patch-clamp recordings were obtained in juvenile male rats to further investigate the actions of PRL at the SFO. Dissociated SFO neurones perfused with 1 μmol L PRL resulted in 2 responsive subpopulations of neurones; 40% depolarised (n = 15/43, 11.3 ± 1.7 mV) and 14% hyperpolarised (n = 6/43, -6.7 ± 1.4 mV) to PRL application. Within the range of 10 pmol L to 1 μmol L , the concentrations of PRL were not significantly different in either the magnitude (P = .53) or proportion (P = .19) of response. Furthermore, PRL application significantly reduced the transient K current in 67% of SFO neurones in voltage-clamp configuration (n = 6/9, P = .02). The stability in response to PRL and expression of PRL-R in the SFO suggests that PRL function is conserved across physiological states and circulating PRL concentrations, prompting further investigations aiming to clarify the nature of PRL function in the SFO.

Amylin and Leptin interaction: Role During Pregnancy, Lactation and Neonatal Development

“…In addition to the amylin-expressing cells in the POA described by Dobolyi, we have also observed amylin immunoreactivity in the subfornical organ, supraoptic nucleus, and ARC of lactating rat dams (unpublished observations). The expression pattern of hypothalamic amylin-producing cells is notably similar to that of prolactin-sensitive cells(Brown et al, 2010;Kamesh et al, 2018).…”

Anatomical Organization of the Rat Subfornical Organ

“…In addition, subpopulations of SFO neurons express receptors for hormones associated with regulating energy metabolism, such as amylin ( Sexton et al, 1994 ; Pulman et al, 2006 ; Smith et al, 2009 ), ghrelin ( Pulman et al, 2006 ), leptin ( Smith et al, 2009 ), cholecystokinin ( Ahmed et al, 2014 ), neuropeptide Y ( Kishi et al, 2005 ), and glucagon-like peptide 1 ( Göke et al, 1995 ), as well as molecules involved in neuroimmune interactions, such as lipopolysaccharide receptor ( Lacroix et al, 1998 ), prostaglandins ( Matsumura et al, 1990 ; Zhang and Rivest, 1999 ), interleukin 1b and interleukin 6 ( Takahashi et al, 1997 ), and TNFα ( Simpson and Ferguson, 2017 ). Moreover, SFO neurons express nitric oxide synthase ( Jurzak et al, 1994 ; Alm et al, 1997 ), relaxin receptors ( Burazin et al, 2005 ), vasopressin V1 receptor ( Phillips et al, 1988 ), atrial natriuretic peptide ( Quirion et al, 1984 ; Mendelsohn et al, 1987 ), estrogen receptor ( Somponpun et al, 2004 ), prolactin receptor ( Kamesh et al, 2018 ), galanin receptor ( O’Donnell et al, 1999 ), and somatostatin ( Patel et al, 1986 ), as well as ion channels such as TRPV1 ( Mannari et al, 2013 ), Na x ( Hiyama et al, 2004 ; Nehmeì et al, 2012 ), and classical neurotransmitter receptors such as glutamate, GABA, and acetylcholine ( McKinley et al, 2003 ). Although it remains unknown whether the expression of these molecules defines distinct neuronal subpopulations within the SFO, these findings are consistent with the involvement of this nucleus in a myriad of centrally regulated homeostatic processes, including energy metabolism and food anticipatory activity ( Pulman et al, 2006 ; Smith and Ferguson, 2010 ), thirst ( Hollis et al, 2008 ), reproduction ( Summerlee et al, 1987 ; Sunn et al, 2002 ), immune responses ( Takahashi et al, 1997 ), cardiovascular regulation ( Cancelliere and Ferguson, 2017 ; Jeong et al, 2019 ; Rossi et al, 2019 ), and systemic osmoregulation ( Oldfield et al, 1994 ).…”