Reproductive neuroendocrine dysfunction in polycystic ovary syndrome: Insight from animal models

Abstract

Polycystic ovary syndrome (PCOS) is a common endocrinopathy with elusive origins. A clinically heterogeneous disorder, PCOS is likely to have multiple etiologies comprised of both genetic and environmental factors. Reproductive neuroendocrine dysfunction involving increased frequency and amplitude of gonadotropin-releasing hormone (GnRH) release, as reflected by pulsatile luteinizing hormone (LH) secretion, is an important pathophysiologic component in PCOS. Whether this defect is primary or secondary to other changes in PCOS is unclear, but it contributes significantly to ongoing reproductive dysfunction. This review highlights recent work in animal models, with a particular emphasis on the mouse, demonstrating the ability of pre- and postnatal steroidal and metabolic factors to drive changes in GnRH/LH pulsatility and GnRH neuron function consistent with the observed abnormalities in PCOS. This work has begun to elucidate how a complex interplay of ovarian, metabolic, and neuroendocrine factors culminates in this syndrome.

A Novel Letrozole Model Recapitulates Both the Reproductive and Metabolic Phenotypes of Polycystic Ovary Syndrome in Female Mice1

“…Moreover, another study reported that glucose tolerance was normal in PNA mice [26]. It has been suggested that the absence of significant metabolic dysfunction or obesity in PNA mice signifies it as a lean PCOS model [73] and could be useful for representing the condition in some PCOS women who lack metabolic impairments [74]. Alternatively, the PNA model may represent a milder form of PCOS across the PCOS spectrum.…”

Steroid Signaling Establishes a Female Metabolic State and Regulates SREBP to Control Oocyte Lipid Accumulation

“…Reproduction in all systems is heavily influenced by metabolism and nutrition [1,2]. Several human reproductive disorders have been linked to malnutrition, diabetes, and obesity [3].…”

An updated view of hypothalamic–vascular–pituitary unit function and plasticity

“…For example, polycystic ovarian syndrome (PCOS), the most common anovulatory cause of infertility 71 affecting >100 million women worldwide, is associated with a dysregulation of the normal pattern of LH secretion 72 . Whether the origin of this multi-factorial disorder is at the level of the hypothalamic-pituitary axis is unknown 73 , but PCOS is characterized by increases in GnRH pulse frequency and sensitivity of the pituitary gland to the neurohormone 74,75 . Consequently, potential interventions that modify the dynamics of GnRH output, its transport to the ME or its 79 .…”