Molecular characterization and brain distribution of the progesterone receptor in whiptail lizards

Abstract

Progesterone and its nuclear receptor are critical in modulating reproductive physiology and behavior in female and male vertebrates. Whiptail lizards (genus Cnemidophorus) are an excellent model system in which to study the evolution of sexual behavior, as both the ancestral and descendent species exist. Male-typical sexual behavior is mediated by progesterone in both the ancestral species and the descendant all-female species, although the molecular characterization and distribution of the progesterone receptor protein throughout the reptilian brain is not well understood. To better understand the gene targets and ligand binding properties of the progesterone receptor in whiptails, we cloned the promoter and coding sequence of the progesterone receptor and analyzed the predicted protein structure. We next determined the distribution of the progesterone receptor protein and mRNA throughout the brain of C. inornatus and C. uniparens by immunohistochemistry and in situ hybridization. We found the progesterone receptor to be present in many brain regions known to regulate social behavior and processing of stimulus salience across many vertebrates, including the ventral tegmental area, amygdala, nucleus accumbens and several hypothalamic nuclei. Additionally, we quantified immunoreactive cells in the preoptic area and ventromedial hypothalamus in females of both species and males of the ancestral species. We found differences between both species and across ovarian states. Our results significantly extend our understanding of progesterone modulation in the reptilian brain and support the important role of the nuclear progesterone receptor in modulating sexual behavior in reptiles and across vertebrates.

The Vertebrate mesolimbic reward system and social behavior network: A comparative synthesis

“…Reptilian vomeronasal information is relayed to the pallial nucleus sphericus and subpallial medial amygdala , and these regions send projections through the stria terminalis to the hypothalamus, as is characteristic of the mammalian meAMY Martinez-Marcos et al, 1999). This reptilian homolog is neurochemically similar to the mammalian meAMY (Table 3) and contains sex steroid hormone receptors (Young et al, 1994;O'Connell et al, 2011c). Additionally, neurochemical evidence supports the subpallial origin of the reptilian meAMY (Table 3) (Moreno et al, 2010).…”

“…The POA contains sex steroid hormone receptors (Young et al, 1994;O'Connell et al, 2011c) and is a central integration point for telencephalic regions and the hypothalamus (Russchen and Jonker, 1988;Smeets et al, 1995). This region is also functionally similar to the mammalian POA, as implants into the POA of either testosterone or DHT in castrated male lizards increase sexual behavior (Morgantaler and Crews, 1978;Rozendaal and Crews, 1989), while lesions of the POA decrease courtship behavior (Kingston and Crews, 1994).…”

“…The reptilian VMH homolog is topographically located along the third ventricle in the ventrocaudal hypothalamus and contains sex steroid hormone receptors (Young et al, 1994;O'Connell et al, 2011c). This region is also highly interconnected with the hypothalamus and amygdaloid nuclei (Bruce and Neary, 1995a,b), and appears to also be functionally similar to the mammalian VMH, as lesions decrease receptivity in female dessert grassland lizards (Cnemidophorus uniparens; Kendrick et al, 1995).…”

“…The reptilian LS shares the mammalian LS trait of unidirectional input from the HIP , contains sex steroid hormone receptors (Young et al, 1994;Beck and Wade, 2009;O'Connell et al, 2011c), and is located medial to the lateral ventricles. Importantly, in reptiles the LS also receives input from the nucleus accumbens (NAcc) and dopaminergic projections from the VTA and sends massive projections to the hypothalamus, providing a functional link between the reward system and the hypothalamic SBN.…”

Neural distribution of the nuclear progesterone receptor in the túngara frog, Physalaemus pustulosus

“…Although our discussion here focuses on two candidate neural networks that appear to regulate social decision-making in vertebrates, Newman's social behavior network (Newman, 1999) and the mesolimbic dopamine system, the wide distribution of PR (Munchrath and Hofmann, 2010), D. rerio (Hanna et al, 2010); reptile: C. inornatus and C. uniparens (O'Connell et al, 2011); bird: T. guttata (Lubischer and Arnold, 1990), G. domesticus (Sterling et al, 1987), songbirds (Gahr, 2001); Mammal: R. norvegicus (Kato et al, 1994), M. musculus (Shughrue et al, 1992), C. porcellus (Warembourg et al, 1986).…”