Reduction of glucose availability suppresses pulsatile luteinizing hormone release in female and male rats.

Abstract

Glucose availability controls reproductive activity through modulation of LH secretion. The aim of the present study was to determine whether the glucoprivic suppression is potentiated by gonadal steroids and if glucoprivic suppression of pulsatile LH release is sexually differentiated. Pulsatile LH secretion was examined in rats after peripheral (jugular) administration of the competitive inhibitor of glycolysis, 2-deoxyglucose (2DG). Fourteen days after gonadectomy, blood samples were collected every 6 min for 3 h. One hour after the onset of sampling, 2DG was administered peripherally (200, 400, or 800 mg/kg BW, iv), and food intake was determined after 2DG injection in gonadectomized males and females in the presence or absence of sex steroids (testosterone or estradiol). To test the ability of the pituitary to produce LH under glucoprivic conditions, LHRH was injected every 30 min for 2.5 h in ovariectomized (OVX) rats 30 min after treatment with 400 mg/kg 2DG. At all peripheral doses of 2DG in females and at the middle and high doses of 2DG in males, mean plasma LH and LH pulse frequency decreased (P < 0.05) in the presence of steroids. However, in the absence of sex steroids, the lowest dose in females and the middle dose in males were not effective. Pituitary function appeared normal, because increases in mean plasma LH in response to the exogenous LHRH occurred in OVX rats treated with the middle dose of 2DG. Food intake significantly (P < 0.05) increased after 2DG injection in all groups except estrogen-treated OVX females at the low and high doses of 2DG. These findings suggest that glucoprivic suppression of LH pulses is potentiated by gonadal steroids in both sexes. Moreover, the hypothalamo-hypophyseal axis of the female rat seems to be more sensitive to the decreased glucose availability induced by 2DG than that of the male.

Evidence for GnRH Regulation by Leptin: Leptin Administration Prevents Reduced Pulsatile LH Secretion during Fasting

“…The glucose availability has been proposed to modulate GnRH secretion [13, 25, 26]. Suppression of pulsatile LH secretion has been documented under low insulin levels despite high glucose levels in streptozotocin-induced diabetic rats [27], though it remains unclear if neural cells monitoring glucose availability to regulate GnRH are sensitive to insulin.…”

Suppressive Action of Orexin A on Pulsatile Luteinizing Hormone Secretion Is Potentiated by a Low Dose of Estrogen in Ovariectomized Rats

“…These studies have shown the existence of a dose-dependent response to orexins, but have also suggested a modulatory role of estrogen in this response. In support of the latter view, there is general agreement that suppressive actions of fasting, insulin injection, and 2-deoxyglucose injection on pulsatile LH secretion are significantly greater in the presence of a small dose of estrogen than in its absence in OVX animals [13, 14, 15, 16]. …”

Changes in Insulin, Glucose and Ketone Bodies, But Not Leptin or Body Fat Content Precede Restoration of Luteinising Hormone Secretion in Ewes

“…Instead of, or in addition to, hormonal signals, signals generated by the oxidation of metabolic fuels are critical for normal reproductive function. For example, inhibition of glucose oxidation inhibits oestrous cyclicity in intact, well‐fed Syrian hamsters (30), alters oestrogen‐receptor distribution and the duration of oestrous behaviour in steroid‐primed, ovariectomised hamsters (31), and suppresses pulsatile LH secretion in well‐fed rats (32) and ewes (33). During food restriction, profound changes in circulating metabolic fuels occur as fuel utilisation shifts from oxidation of carbohydrates derived from ingested food and liver glycogen to utilisation of fuels from long‐term stores of lipids in adipose tissue.…”