Investigation of the Mechanism by which Insulin-Induced Hypoglycemia Decreases Luteinizing Hormone Secretion in Ovariectomized Ewes*

Abstract

Ovariectomized ewes were treated with 100 IU insulin, iv, which caused reductions in blood sugar and plasma LH concentrations. The effect was prevented by the infusion (iv) of glucose, suggesting that neuroglycopenia and not a direct action of insulin was the cause of reduced LH secretion. An iv infusion of naloxone (40 mg/h for 2 h), which commenced 25 min before the insulin injection, blocked the inhibitory effect of insulin on LH secretion, but it did not prevent the decrease in plasma glucose concentrations. In this treatment group and in a group treated only with naloxone, the opioid antagonist significantly stimulated LH secretion. To determine whether CRF might be involved in the insulin-induced decrease in LH secretion, 50 micrograms CRF were injected into ovariectomized sheep. Despite producing very high circulating concentrations of CRF within 2 min of injection and the stimulation of cortisol secretion during most of the 4-h posttreatment period, plasma LH levels were not affected. In addition, the intracerebroventricular administration of 10 micrograms CRF or 10 micrograms CRF plus 10 micrograms arginine vasopressin (AVP) did not affect LH secretion. These observations suggest that insulin-induced hypoglycemia decreased LH secretion by neuroglycopenia. This may involve an opioidergic mechanism, but does not involve activation of the hypothalamo-pituitary-adrenocortical axis.

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.…”

“…Treatment of ovariectomized ewes with 1-2 mg dexamethasone once a day for 14 days did not decrease the secretion of LH or inhibit the LH response to GnRH (Phillips and Clarke, 1990), neither did cortisol nor dexamethasone treatment affect the generation of the LH surge in ewes (Phillips and Clarke, 1990). In rams, an infusion of 2-4 mg cortisol min -1 for 9 h did not affect the LH response to GnRH (Fuquay and Moberg, 1983).…”

Simultaneous Observation of the GnRH Pulse Generator Activity and Plasma Concentrations of Metabolites and Insulin during Fasting and Subsequent Refeeding Periods in Shiba Goats

“…Several lines of evidence suggest that blood-borne energy substrates or metabolic hormones, such as insulin, signal the mechanism generating pulsatile GnRH and LH release to control gonadal activity [8][9][10]. Insulin-induced hypoglycemia inhibits pulsatile LH secretion in rats [11,12], sheep [13,14], a n d m o n k e y s [ 1 5 , 1 6 ] . P h a r m a c o l o g i c a l glucoprivation with the administration of 2-deoxy-D-g lucose (2DG), a competitive inhibitor of intracellular glucose oxidation, suppresses pulsatile LH secretion in rats [17,18] and sheep [19].…”

Supplementation of lactating ewes with a glucogenic preparation or β-carotene in mid- to late lactation, on subsequent milk yield and luteinizing hormone secretion

“…As mentioned, plasma concentration of glucose has been found to peak quickly after oral drenching of propylene glycol, subsequently returning to pre-administration levels (Nielsen and Ingvartsen 2004). It is also known that the effects of metabolic challenges on LH pulsatility occur far more rapidly than changes to body fat content in sheep (Clarke et al 1990;Schneider 2004). In the present study, the duration and the dose of glucogenic administration were sufficient to maintain, but not to increase body weight; this could be a reason for the lack of effects in LH parameters.…”

“…Even short-term manipulation of energy availability can affect LH secretion. It has been shown that acute insulin-induced hypoglycemia resulted in depressed LH secretion and the decrease in LH was prevented by infusion of glucose (Clarke et al 1990). Similarly, feed restrictions may have a substantial effect on plasma gonadotropin concentrations, reducing LH secretion to a level that would result in blocking reproductive function (Foster et al 1989).…”