Evidence That GnRH Decreases with Gonadal Steroid Feedback but Increases with Age in Postmenopausal Women

Abstract

1) The overall quantity of GnRH secretion increases with age as demonstrated by the progressive decrease in LH inhibition following submaximal GnRH antagonist administration with increasing age; 2) E negative feedback is associated with a decrease in GnRH secretion (as indicated by an increased percent inhibition of LH following submaximal GnRH receptor blockade); 3) E2 and P are associated with a further decease in overall amount of GnRH secreted; and 4) Age does not dampen the inhibition of hypothalamic GnRH secretion by E and P in PMW.

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

“…These ®ndings agree with the demonstration of increased GnRH mRNA in the basal hypothalamus of orchidectomized rhesus monkeys (35) and, conversely, suppression of hypothalamic GnRH mRNA by oestrogen in the ovariectomized female monkey (31,36). Using indirect pharmacological methods, Gill et al (12) showed that oestrogen negative feedback on GnRH secretion is still preserved in older women. In summary, these ®ndings suggest that ovarian failure is an important factor contributing to the rise in hypothalamic GnRH gene expression and gonadotropin hypersecretion in postmenopausal women (7).…”

“…Another cleavage product of POMC, a-melanocyte-stimulating hormone, reduces food intake through its interactions at multiple hypothalamic sites (9,11). Thus, a decline in the activity of hypothalamic POMC neurones could contribute to the increased GnRH and luteinizing hormone (LH) secretion (12), as well as the increase in body weight that has been described in older women (13).…”

Synaptic distributions of pS214‐tau in rhesus monkey prefrontal cortex are associated with spine density, but not with cognitive decline

“…Tests used in rhesus monkeys are similar to, if not the same as, those used to assess cognitive status in humans (Nagahara, Bernot, & Tuszynski, 2010;Squire, Zola-Morgan, & Chen, 1988). Brain anatomy, neuronal gene expression, reproductive physiology, and progression of endocrine senescence of rhesus macaques are also similar to those of humans (Gill, Sharpless, Rado, & Hall, 2002;Loerch et al, 2008;Matt, Kauma, Pincus, Veldhuis, & Evans, 1998;Nichols et al, 2005;Petrides & Pandya, 1999;Walker & Herndon, 2008;Woller et al, 2002). Though relatively later in life, rhesus monkeys undergo a low-estrogen menopause that is qualitatively similar to that in women (Gilardi, Shideler, Valverde, Roberts, & Lasley, 1997;Nichols et al, 2005;Walker & Herndon, 2008).…”

Attenuation of the oestrogen positive feedback mechanism with the age in postmenopausal women

“…11,12 Despite this, evidence has been provided that there is an agerelated increase in the hypothalamic content of GnRH, although the pulse frequency decreases. 13,28 This discrepancy between hypothalamic and pituitary hormones is difficult to explain. Nevertheless, not only basal LH but also the LH response to GnRH decreases with age, 14 indicating the possible existence of a short-loop feedback mechanism operating locally between the pituitary and hypothalamus.…”

“…11,12 This decline seems not to be related to reduced hypothalamic stimulation of the pituitary, via GnRH, as the production of GnRH appears to increase with increasing age. 13 As the in vivo response of the two gonadotropins to a GnRH stimulus is attenuated in later as compared to early postmenopausal years, 14 it is more likely that the reduced production of gonadotrophins is due to the ageing process that affects the functional capacity of several body organs including the pituitary. Whether this could also imply a change in the oestrogen-induced positive feedback mechanism with the age is not known.…”