Effects of Ovariectomy on the Neuroendocrine Axes Regulating Reproduction and Energy Balance in Young Cynomolgus Macaques

Abstract

Degeneration of the ovary in middle-aged women results in castrate levels of ovarian steroids and increased gonadotropin secretion from the anterior pituitary gland. Ageing in women is also accompanied by significant changes in energy homeostasis. We have observed alterations in hypothalamic morphology and gene expression in older women, including hypertrophy and increased gene expression of neurokinin B (NKB) neurones, elevated levels of gonadotropin releasing-hormone (GnRH) mRNA and decreased numbers of neurones expressing pro-opiomelanocortin (POMC) mRNA. To determine if loss of ovarian steroids could produce comparable changes in gene expression in young primates, we measured the effects of ovariectomy on NKB, GnRH and POMC gene expression in young cynomolgus monkeys. We also measured serum leptin and body weight to examine the consequences of ovariectomy on energy balance. NKB neurones in the infundibular nucleus of ovariectomized monkeys were larger, more numerous and displayed increased levels of NKB mRNA compared to those of intact controls. Moreover, ovariectomy increased the number of neurones expressing GnRH gene transcripts and elevated serum luteinizing hormone. By contrast, several parameters related to energy balance, including POMC gene expression, serum leptin and body weights, were unchanged by ovariectomy. Thus, the rise in NKB and GnRH gene expression in older women was simulated by ovariectomy in monkeys, but the changes in POMC gene expression and energy balance were not. This study provides strong support for the hypothesis that ovarian failure contributes to the increased NKB and GnRH gene expression observed in postmenopausal women.

Tachykinins and tachykinin receptors: effects in the genitourinary tract

“…Both actions have been proposed to be dependent on gonadal steroids. Orchidectomy in male animals and ovariectomy in females increase mRNA levels of TAC3 (the gene that encodes NKB) in the arcuate nucleus, an effect similar to that reported in aging men with decreased gonadal function (Rance and Bruce, 1994;Danzer et al, 1999;Sandoval-Guzman et al, 2004). This increase in TAC3 expression parallels that occurring in postmenopausal women (Rance and Young, 1991).…”

Hypertrophy and Increased Kisspeptin Gene Expression in the Hypothalamic Infundibular Nucleus of Postmenopausal Women and Ovariectomized Monkeys

“…The endocrine status of these monkeys has been described previously (5). Animal treatments were carried out in compliance with state and federal laws, standards of the Department of Health and Human Services, and the guidelines of the Institutional Animal Care and Use Committee at the Wake Forest School of Medicine and the University of Arizona.…”

Ablation of KNDy Neurons Results in Hypogonadotropic Hypogonadism and Amplifies the Steroid-Induced LH Surge in Female Rats

“…Research into the function of KNDy neurons has been facilitated by the identification of a homologous group of neurons in the arcuate nucleus of the monkey (7,8,17,18), sheep (19), goat (20), rat (21,22), and mouse (23). To date, there is evidence that KNDy neurons mediate estrogen negative feedback on LH secretion, relay progesterone (P) inhibition of pulsatile GnRH secretion and modulate the pulsatile release of GnRH (5, 24 -26).…”