Hypoglycemic ‘Stress’ and Gonadotropin-Releasing Hormone Pulse Generator Activity in the Rhesus Monkey: Role of the Ovary

Abstract

Observations of long standing have suggested that the ‘stress’ of chair restraint inhibits the GnRH pulse generator in normal female monkeys while this phenomenon is rarely observed in ovariectomized animals. The role of the ovary in the response of the GnRH pulse generator to the stress of insulin hypoglycemia was investigated in both intact and ovariectomized rhesus monkeys. Following an overnight fast the animals, previously habituated to restraint, were placed in primate chairs and GnRH pulse generator activity monitored electrophysiologically. Insulin-induced reductions in mean blood glucose concentrations of 10-40% of control values interrupted pulse generator activity in intact monkeys but were without effect in ovariectomized animals. With larger reductions in blood glucose, pulse generator activity was interrupted in both groups but the inhibition was twice as long in intact than in ovariectomized animals. The reduced responsiveness of ovariectomized animals to insulin hypoglycemia was significantly reversed by estradiol replacement. Naloxone administration did not prevent the hypoglycemia-induced inhibition of pulse generator activity in either intact or ovariectomized rhesus monkeys. It is concluded that hypoglycemic ‘stress’ inhibits the GnRH pulse generator by a nonopioidergic mechanism and that ovarian products, most probably estradiol, exacerbate this effect.

Effects of stress on reproduction in non-rodent mammals: the role of glucocorticoids and sex differences

“…Similar effects were found in gonadectomized rams and ewes during 4 h of isolation and restraint (Tilbrook et al, 1999), in sheep after injection of insulin (Clarke et al, 1990) or endotoxin (Battaglia et al, 1998), in ovariectomized rhesus monkeys after injection of insulin (Chen et al, 1992) and in male (Norman and Smith, 1992) and female (Norman et al, 1994) rhesus monkeys after 6 h of restraint. A number of studies have also investigated the effects of repeated acute stress on LH secretion.…”

“…In female rhesus monkeys that were restrained in a chair for sampling, LH pulses (Dierschke et al, 1970) and hypothalamic multiunit electrical activity (Wilson et al, 1984) were detected in ovariectomized but not intact animals. Insulininduced hypoglycaemia inhibited hypothalamic multiunit electrical activity to a greater extent in intact than in ovariectomized animals and this reduced responsiveness in the ovariectomized females was reversed when they were treated with oestradiol (Chen et al, 1992). Moreover, when female rhesus monkeys were subjected to 6 h of chair restraint, plasma LH concentrations were suppressed during the follicular phase but not during the luteal phase of the menstrual cycle (Norman et al, 1994).…”

The effects of intensive, long-term treadmill running on reproductive hormones, hypothalamus–pituitary–testis axis, and semen quality: a randomized controlled study

“…The stress response in the neuroendocrine system includes release of corticotropin-releasing hormone (CRH) from the hypothalamic paraventricular nucleus and the secretion of pituitary ACTH, leading to the secretion of glucocorticoid hormones by the adrenal cortex (Carrasco & Van de Kar 2003). In response to strenuous exercise, there is an enhanced secretion of cortisol, stimulated by increased release of ACTH, which serves to mobilize fuel stores (Deuster et al 1989) and CRH-induced proopiomelanocortin peptides, such as b-endorphin, and inhibits hypothalamic GnRH secretion (Chen et al 1992). In addition, glucocorticoids suppress gonadal axis function at the hypothalamic-pituitary level (Sakakura et al 1975).…”

Suppression of the secretion of luteinizing hormone due to isolation/restraint stress in gonadectomised rams and ewes is influenced by sex steroids

“…In female rhesus monkeys that were restrained in a chair for sampling, LH pulses (Dierschke et al 1970) and hypothalamic multiunit electrical activity (Wilson et al 1984) were detected in ovariectomised but not intact animals. Insulin-induced hypoglycaemia inhibited hypothalamic multiunit electrical activity to a greater extent in intact than in ovariectomised animals and this reduced responsiveness in the ovariectomised females was reversed when they were treated with oestradiol (Chen et al 1992). Moreover, when female rhesus monkeys were stressed by 6 h of chair restraint the levels of LH were suppressed in the follicular phase but not in the luteal phase of the menstrual cycle (Norman et al 1994).…”