Effect of Environmental Toxicants on the Neuroendocrine Control of Female Reproduction

Hypothalamic gonadotropin releasing hormone is the primary signal regulating the release of pituitary gonadotropins for reproductive function, specifically gametogenesis and gonadal sex steroid synthesis. Feedback signals from the gonads (sex steroids) communicate with the hypothalamic-pituitary axis to maintain gonadal function.  Environmental toxicants can target this system and disrupt the timing and amount of pituitary hormone secretion ultimately impairing ovarian function, estrous cyclicity and ovulation. This type of neuroendocrine disruption of the complex hypothalamic regulation of gonadotropin releasing hormone can also delay puberty when chemical exposures occur during key developmental windows. This chapter will provide an overview of the hypothalamic regulation of these reproductive processes and provide examples of the disruption of neuroendocrine regulation by exposure to environmental chemicals. 

Impact/Purpose

The endocrine system regulates cell signaling via specific hormones released into the bloodstream to interact with receptors in other tissues.  Neuroendocrinology is the study of the involvement of the central nervous system (CNS), mainly in the hypothalamus, to regulate pituitary hormone release and ultimately target organ responses.  The hypothalamus is located at the base of the brain and accounts for less than one percent of the total brain weight.  The neuroendocrine system is responsible for many critical functions, including energy and temperature homeostasis, circadian rhythms, as well as the primary control center for reproduction and reproductive behavior.  The regulation of the hypothalamic-pituitary-gonadal (HPG) axis controls reproductive function of both sexes.  In the female, the hypothalamus integrates sensory and ovarian steroid hormone input to modulate the activity of neurons that synthesize and release gonadotropin-releasing hormone (GnRH), which in turn governs the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the pituitary. Disruption of GnRH secretion as any time during development by exposure to environmental toxicants can cause both transient and permanent effects on fertility.  Such effects can be mediated by a direct action of the chemical on the GnRH neurons or indirectly by impairing the release or activity of hypothalamic neurotransmitters or neuropeptides of neurons that regulate GnRH secretion. Although most studies in this area have used rodent models, non-human primate and human reproductive systems share several common characteristics with the mouse and rat. These mammals all have a mid-cycle gonadotropin surge that triggers follicular development and maturational changes of the oocyte within the ovary as well as spontaneous ovulation. 

Citation

Stoker, T. Effect of Environmental Toxicants on the Neuroendocrine Control of Female Reproduction. ELSEVIER, AMSTERDAM, HOLLAND4.00118-2, (2024). [DOI: 10.1016/B978-0-323-95488-4.00118-2]

DOI: Effect of Environmental Toxicants on the Neuroendocrine Control of Female Reproduction