Impact of the opioid system on the reproductive axis

Abstract

Endogenous opioids, first described more than 40 years ago, have long been recognized for their main role as important neuromodulators within the central nervous system. More recently endogenous opioids and their receptor have been identified in a variety of reproductive and nonreproductive tissues outside the central nervous system. Their role within these tissues and organs, however, is only incompletely understood. In the central nervous system, endogenous opioids inhibit pulsatile GnRH release, in part mediating the stress response within the central nervous-pituitary gonadal axis, resulting in hypothalamic amenorrhea. In the ovary, the presence of endogenous opioids primarily produced by granulosa cells has been demonstrated within the follicular fluid, likely influencing oocyte maturation. In hypothalamic amenorrhea, normal cycles can be restored by the administration of opioid antagonists, such as naltrexone. In polycystic ovarian syndrome, endogenous opioids have found to be elevated and may stimulate insulin secretion from the endocrine pancreas. This effect can be inhibited by opioid antagonists, resulting in a decrease of circulating insulin levels in response to glucose challenge. Endogenous opioids may also play a role in the pathogenesis of ovarian hyperstimulation syndrome. In summary, endogenous opioids exert a wide variety of actions within the reproductive system and are worthy of further scientific study.

Phosphoproteomic and Functional Analyses Reveal Sperm-specific Protein Changes Downstream of Kappa Opioid Receptor in Human Spermatozoa

“…Finally, the opioid system is known to be involved in regulating carbohydrate metabolism and immune system functions in the periphery (62,63). This is consistent with the phosphorylation changes we observe in the metabolic enzymes like PGK1 and PGK2, which are implicated in an important step of the glycolysis (64), and hence in sperm fertility (65).…”

The immune-opioid axis in prediabetes: prediction of prediabetes with insulin resistance by plasma interleukin-10 and Endomorphin-2 to kappa-opioid receptors ratio

“…The opioid system manages the endocrine function of β-cells [40]. Within the pancreas, EOPs result in insulin secretion via the paracrine and the intracrine mechanisms [41]. Opioid activity can perform an important role in the physiopathology of hyperinsulinemia in hyperandrogenic women [38].…”

Functional hypothalamic amenorrhea: case presentations and overview of literature

“…Thus, the etiology of her amenorrhea was weight loss in the context of systemic illness, compounded by narcotics. Narcotic analgesics shut off the GnRH pulse generator and the pituitary-ovarian axis is also thus shut off [7], a finding that was illustrated many years ago [8]. Using electrodes implanted in the mediobasal hypothalamus of the ovariectomized rhesus monkey to record multiunit activity, with simultaneous measurement of serum LH, it was shown that a single 2-min intravenous infusion of morphine (2 mg per kg body weight) shuts down multiunit electrical activity of the pulse generator and the corresponding LH pulses, this effect lasting at least 4 h. The outcome is the same as that of endogenous opioids such as β-endorphin that are produced in response to stress and exercise.…”