Projects / Programmes
Role of estrogens in active brain feminisation; and development of a novel hormone implant,
mimicking estrous cycle
| Code |
Science |
Field |
Subfield |
| 4.04.00 |
Biotechnical sciences |
Veterinarian medicine |
|
| Code |
Science |
Field |
| B000 |
Biomedical sciences |
|
| Code |
Science |
Field |
| 4.03 |
Agricultural and Veterinary Sciences |
Veterinary science |
brain, feminization, sexual behavior, parental behavior, estrogens, hormone implants
Researchers (8)
Organisations (2)
Abstract
Classical hypothesis of brain sexual differentiation suggest that testosterone, secreted from testes during fetal and early postnatal periods, affects male brain to become masculinized and defeminized. However, there is an important, yet unanswered question whether development of a female brain is a default pathway without any hormonal influences, or is there a mechanism for active feminization of the female brain. Some studies in recent years have hinted that in rodents prepubertal period between days 15 to 25 is important period for active feminization of the female brain by low amounts of estrogens secreted from the ovary before puberty. In the proposed studies we will further explore this hypothesis, using hormonally/pharmacologically manipulated WT mice and agonadal SF-1 KO mice. WT female mice will be ovariectomized on day 10 and will be given supplemental estrogens or agonists of estrogen receptors alpha and beta (PPT and DPN, respectively). Similarly, agondal SF-1 KO mice will be treated with estradiol during the period from day 15 until day 25 of postnatal life. Mice will be examined in adult life for typical female behaviors such as female sexual behavior and maternal behavior, and some tests modeling sexually dimorphic psychiatric disorders. After testing, mice will be sacrificed and their brains will be used for immunohistochemistry and/or RNA extractions to determine differences in gene expression of target genes that might be caused by different treatments in prepubertal period. As a separate workpackage, we will develop a novel implant for mimicking estrous cycle that will be initially used in behavioral studies in rodents instead of currently used silastic implants or estradiol pellets. However, such implant mimicking estrous cycle will be later translated also into clinical human medicine as a novel, more physiological approach to hormone replacement therapy.
Significance for science
The results will be highly relevant for behavioral neuroscience as well as clinical medicine. Results about feminization of the female brain will shed important information about sexual differentiation of the brain, what is important for understanding many psychiatric diseases that show sex differences in prevalence and/or clinical manifestation. The product developed in WP3 will be directly commercially exploitable as such product will be the first product of its kind enabling better, in particular more physiological mimicking of estrous cycle in behavioral research. However, much wider application of such implant will be in clinical human medicine as such implant could replace classical hormone replacement therapy in menopausal women, ensuring replacement of hormones in more physiological and thus most likely safer way. Of course, to implement such novel device in clinical medicine it will have to be developed and tested in clinical trials in subsequent years, but after successful completion of this implant for rodents, we will seek collaboration with suitable pharmaceutical company (we already have one potential company with whom we are collaborating on other projects) to speed up the implementation of such implant into clinical medicine.
Significance for the country
The results will be highly relevant for behavioral neuroscience as well as clinical medicine. Results about feminization of the female brain will shed important information about sexual differentiation of the brain, what is important for understanding many psychiatric diseases that show sex differences in prevalence and/or clinical manifestation. The product developed in WP3 will be directly commercially exploitable as such product will be the first product of its kind enabling better, in particular more physiological mimicking of estrous cycle in behavioral research. However, much wider application of such implant will be in clinical human medicine as such implant could replace classical hormone replacement therapy in menopausal women, ensuring replacement of hormones in more physiological and thus most likely safer way. Of course, to implement such novel device in clinical medicine it will have to be developed and tested in clinical trials in subsequent years, but after successful completion of this implant for rodents, we will seek collaboration with suitable pharmaceutical company (we already have one potential company with whom we are collaborating on other projects) to speed up the implementation of such implant into clinical medicine.
Most important scientific results
Interim report
Most important socioeconomically and culturally relevant results
