Estrogens, Conjugated Synthetic B(Teva Pharmaceutical Industries Ltd.)

In humans, exposure to early life adversity has profound implications for susceptibility to developing neuropsychiatric disorders later in life. Studies in rodents have shown that stress experienced during early postnatal life can have lasting effects on brain development. Glucocorticoids and sex steroids are produced in endocrine glands and the brain from cholesterol; these molecules bind to nuclear and membrane-associated steroid receptors. Unlike other steroids that can also be made in the brain, neurosteroids bind specifically to neurotransmitter receptors, not steroid receptors. The relationships among steroids, neurosteroids, and stress are multifaceted and not yet fully understood. However, studies demonstrating altered levels of progestogens, androgens, estrogens, glucocorticoids, and their neuroactive metabolites in both developmental and adult stress paradigms strongly suggest that these molecules may be important players in stress effects on brain circuits and behavior. In this review, we discuss the influence of developmental and adult stress on various components of the brain, including neurons, glia, and perineuronal nets, with a focus on sex steroids and neurosteroids. Gaining an enhanced understanding of how early adversity impacts the intricate systems of brain steroid and neurosteroid regulation could prove instrumental in identifying novel therapeutic targets for stress-related conditions.

In aquatic ecosystems, endocrine-disrupting compounds (EDCs) pose a growing concern for their potential adverse effects on fish reproduction and development. In lake Pyhäjärvi, located in the urban boreal region of Tampere, Finland, a significant number of sexually immature pikeperch (Sander lucioperca) individuals have been identified in size and age categories that are expected to be sexually mature. To explore if this phenomenon is attributed to estrogenic endocrine disruption, we conducted a comprehensive study comparing fish from lake Pyhäjärvi with those from a nearby reference lake, lake Näsijärvi. Roach (Rutilus rutilus), known for its susceptibility to EDCs, was also included for comparison. We examined various parameters in both pikeperch and roach, including size, condition factor, age, reproductive indicators, biometric indices and gonadal histology. We also assessed liver vitellogenin mRNA levels and genetic sex in roach, and measured estrogen levels in lake waters and wastewater treatment plant effluents. Results revealed that approximately one-third of fish in both species exhibited sexual immaturity in lake Pyhäjärvi, with a female-biased sex ratio. Surprisingly, we found no signs of estrogenic endocrine disruption, indicated by the absence of intersex fish in both species. Furthermore, vitellogenin levels in roach closely resembled those in the reference lake. Estrogens were undetectable in the lake waters, suggesting that factors other than estrogenic EDCs, including other potential endocrine disruptors such as PCBs or heavy metals, may be influencing delayed sexual maturity and skewed sex ratios. Further inquiry is needed to pinpoint these underlying causes. Our study provides essential baseline information on fish sexual development in lake Pyhäjärvi, emphasizing the need for ongoing monitoring and research to understand delayed sexual maturity and biased sex ratios. This is vital given the increasing concern about EDC impacts on aquatic ecosystems and the necessity for effective management strategies to protect these ecosystems' health and integrity.