Farrar, V. S. | Search bioRxiv

bioRxiv2021

Prolactin and prolactin receptor expression in the HPG axis and crop sac during parental care in both sexes of a biparental bird (Columba livia)

During breeding, multiple circulating hormones, including prolactin, facilitate reproductive transitions in species that exhibit parental care. Prolactin underlies parental behaviors and related physiological changes across many vertebrates, including birds and mammals. While circulating prolactin levels often fluctuate across breeding, less is known about how relevant target tissues vary in their prolactin responsiveness via prolactin receptor (PRLR) expression. Recent studies have also investigated prolactin (PRL) gene expression outside of the pituitary (i.e., extra-pituitary PRL), but how PRL gene expression varies during parental care in non-pituitary tissue (e.g., hypothalamus, gonads) remains largely unknown. Further, it is unclear if and how tissue-specific PRL and PRLR vary between the sexes during biparental care. To address this, we measured PRL and PRLR gene expression in tissues relevant to parental care, the endocrine reproductive hypothalamic-pituitary-gonadal (HPG) axis and the crop (a tissue with a similar function as the mammalian mammary gland), across various reproductive stages in both sexes of a biparental bird, the rock dove (Columba livia). We also assessed how these genes responded to changes in offspring presence by adding chicks mid-incubation, simulating an early hatch when prolactin levels were still moderately low. We found that pituitary PRL expression showed similar increases as plasma prolactin levels, and detected extra-pituitary PRL in the hypothalamus, gonads and crop. Hypothalamic and gonadal PRLR expression also changed as birds began incubation. Crop PRLR expression correlated with plasma prolactin, peaking when chicks hatched. In response to replacing eggs with a novel chick mid-incubation, hypothalamic and gonadal PRL and PRLR gene expression differed significantly compared to mid-incubation controls, even when plasma prolactin levels did not differ. We also found sex differences in PRL and PRLR that suggest gene expression may allow males to compensate for lower levels in prolactin by upregulating PRLR in all tissues. Overall, this study advances our understanding of how tissue-specific changes in responsiveness to parental hormones may differ across key reproductive transitions, in response to offspring cues, and between the sexes.

animal behavior and cognition↗

bioRxiv2020

Isolating the role of corticosterone in the hypothalamic-pituitary-gonadal genomic stress response

The negative impacts of stress on reproduction have long been studied. A large focus of investigation has centered around the effects of the adrenal steroid hormone corticosterone (CORT) on a system of tissues vital for reproduction, the hypothalamus of the brain, the pituitary gland, and the gonads (the HPG axis). Investigations of the role of CORT on the HPG axis have predominated the stress and reproductive biology literature, potentially overshadowing other influential mediators. To gain a more complete understanding of how elevated CORT, characteristic of the stress response, affects the activity of the HPG axis, we experimentally examined its role at the level of the genome in both male and female rock doves (Columba livia). We exogenously administrated CORT to mimic circulating levels during the stress response, specifically 30 min of restraint stress, an experimental paradigm known to increase circulating corticosterone in vertebrates. We examined all changes in genomic transcription within the HPG axis as compared to both restraint-stressed birds and vehicle-injected controls, as well as between the sexes. We report causal and sex-specific effects of CORT on the HPG stress response at the level of the transcriptome. Restraint stress caused 1567 genes to uniquely differentially express while elevated circulating CORT was responsible for the differential expression of 304 genes. Only 108 genes in females and 8 in males differentially expressed in subjects who underwent restraint stress and those who were given exogenous CORT. In response to CORT elevation characteristic of the stress response, both sexes shared the differential expression of 5 genes, KCNJ5, CISH, PTGER3, CEBPD, and ZBTB16, all located in the pituitary. The known functions of these genes suggest potential influence of elevated CORT on immune function and prolactin synthesis. Gene expression unique to each sex indicated that elevated CORT affected more gene transcription in females than males (78 genes versus 3 genes, respectively). To our knowledge, this is the first study to isolate the role of CORT in HPG genomic transcription during a stress response. These results provide novel targets for new lines of further investigation and therapy development. We present an extensive and openly accessible view of the role corticosterone in the HPG genomic stress response, offering novel gene targets to inspire new lines of investigation of stress-induced reproductive dysfunction. Because the HPG system is well-conserved across vertebrates, these data have the potential to inspire new therapeutic strategies for reproductive dysregulation in multiple vertebrate systems, including our own.

physiology↗