Biochemical and Biophysical Research Communications
Tamoxifen activates hypothalamic l-dopa synthesis to stimulate ovarian estrogen production in chicken
Introduction
Avian species are an important comparative vertebrate model for the research in endocrinology and reproductive biology. The chicken is also one of the most important agricultural animals, producing 1.1 trillion eggs per year [1]. Thus, studying the physiology of chicken reproduction could benefit both the understanding of basic reproductive biology and the improvement of food industry.
As in other vertebrates, the female avian reproductive systems are primarily regulated by the hypothalamus-pituitary-gonadal axis [2]. The hypothalamus produces gonadotropin-releasing hormone (GnRH) that stimulates pituitary production of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which in turn direct the ovarian function and reproductive activity. Ovarian derived steroids, predominantly estrogen and progesterone, return to the central nervous system through the bloodstream and provide a feedback to the hypothalamic GnRH production and release. It is well known that in birds, estrogen plays a central role in the female reproduction by stimulating ovary and follicle development [3,4]. The effects of estrogen in the target cells are mediated by estrogen receptors (ER), which are expressed not only in the hypothalamus and pituitary but also in ovary and oviduct of chicken. Once activated by estrogen, the ER is able to translocate into the nucleus and bind to DNA to regulate the activity of different genes [5].
Tamoxifen (TAM) is a synthetic estrogen antagonist that could inhibit the transcription of target genes by binding to ER and has been widely used in the therapy for cancer patients with ER-positive tumours [6]. Previous studies in birds have confirmed that TAM could bind to chicken ER with high affinity and limit the transcription of estrogen-induced genes [[7], [8], [9]]. Therefore, TAM was frequently employed to investigate the roles of ER in different chicken tissues by loss-of-function means.
Here we show that TAM treatment in reproductive active chicken resulted in the disruption of laying, which may mainly attribute to the lowered FSH and LH. In contrast, the estrogen levels increased in both ovary and serum. Genome-wide transcriptome analysis of hypothalamus revealed that the hypothalamic l-dopa synthesis was enhanced by TAM treatment. Furthermore, we provide novel evidence that l-dopa could stimulate estrogen production in the undifferentiated but not differentiated follicles in the ovary. We reason that blocking ER leads to enhanced hypothalamic l-dopa synthesis, which in turn stimulates estrogen production in the ovary.
Section snippets
Animals and reagents
Sexually mature (older than 23 weeks) Hy-Line Brown hens were collected from a local research farm affiliated with Taishan University. All animals had free access to water and feed. The hens were housed in separate cages under a daily light period of 14 h and the laying events were recorded by checking the cage every 2 h during the light period to determine the regular laying sequence. For the tamoxifen (TAM) experiment, the control group (n = 6) animals were treated subcutaneously with vehicle
Tamoxifen treatment blocks ovulation and inhibits follicle development
Daily treatment of laying hens with tamoxifen (TAM) caused a gradual decrease of the egg-laying rate from the first day of the experiment. On day 6, all the animals in the TAM treated group stopped laying whereas the control animals continue to lay normally (Fig. 1A). All the animals were sacrificed on day 7 of the experiment. The normal mature chicken ovary was mainly composed of the stroma tissue containing small white and small yellow follicles (undifferentiated follicles) and hierarchical
Discussion
In chicken, the tamoxifen (TAM), are very potent antagonists of estrogen action and manifest very little agonistic activity compared to their action in other species [14]. Therefore, it has been frequently used as loss-of-function means to investigate estrogen action in birds [[15], [16], [17]]. In consistent with previous study, treatment of hens with TAM resulted in cessation of laying and reduction in the number and weight of the hierarchical follicles [18,19]. Our data indicate that this
Acknowledgements
This study was supported by the National Natural Science Foundation of China (31301974) and the Natural Science Foundation of Shandong Province (ZR2013CQ002).
References (31)
- et al.
Alterations in apoptotic markers and egg-specific protein gene expression in the chicken oviduct during pause in laying induced by tamoxifen
Theriogenology
(2018) Control of the reproductive axis: balancing act between stimulatory and inhibitory inputs
Poult. Sci.
(2015)- et al.
Dopamine neuron systems in the brain: an update
Trends Neurosci.
(2007) Interactions of tamoxifen in the chicken
J. Steroid Biochem.
(1987)- et al.
Antiestrogen-induced alterations of hypothalamic dopamine and norepinephrine levels in the female rat
Neuropharmacology
(1981) - et al.
Molecular characterization and differential expression of multiple goose dopamine D2 receptors
Gene
(2014) - et al.
Dopamine receptors in equine ovarian tissues
Domest. Anim. Endocrinol.
(2005) N.R.C. NRC, Critical Role of Animal Science Research in Food Security and Sustainability
(2015)- et al.
Endocrinology of the avian reproductive system
J. Avian Med. Surg.
(1995) Reproduction in the female
The avian ovary and follicle development: some comparative and practical insights
Turk. J. Vet. Anim. Sci.
Two functionally different protein isoforms are produced from the chicken estrogen receptor-α gene
Mol. Endocrinol.
Development of antiestrogens and their use in breast cancer: eight chain memorial award lecture
Canc. Res.
A synthetic oestrogen antagonist, tamoxifen, inhibits oestrogen-induced transcriptional, but not post-transcriptional, regulation of gene expression
Biochem. J.
Tamoxifen advances puberty in the white leghorn hen
Br. Poult. Sci.
Cited by (3)
Synthesis, Regulatory Factors, and Signaling Pathways of Estrogen in the Ovary
2023, Reproductive SciencesINFLUENCE OF NEUROGLUTAM - NEW MEDICINE WITH ANXIOLYTIC AND ANTIDEPRESSANT EFFECT - ON THE SEXUAL BEHAVIOR AND FERTILITY OF FEMALE RATS
2020, Eksperimental'naya i Klinicheskaya Farmakologiya
- 1
These authors contributed equally to this work.