Underfeeding Alters the Effect of Low Levels of Estradiol on Luteinizing Hormone Pulsatility in Ovariectomized Female Rats

Abstract

Reduced food intake results in altered reproductive function in female mammals and previous studies have shown this to be due, at least in part, to an increase in the negative feedback efficacy of estrogen on pituitary luteinizing hormone (LH) secretion. This study attempted to elucidate the site (CNS vs. pituitary) of increased negative feedback efficacy of 17β-estradiol (E₂) in underfed female rats. Rats (Holtzman) were fed either ad libitum (CR) or 50% of normal food intake (UR). All other conditions were identical for CR and UR. When UR stopped exhibiting vaginal cycles, they were ovariectomized (OVX) along with the CR exhibiting normal vaginal cycles, and implanted subcutaneously with Silastic capsules containing 0, 1.2, 2.4 or 4.8 µg E₂. Six or 12 days after OVX, rats were cannulated in the left carotid artery under brief ether anesthesia. Starting 3 h after surgery, blood was collected sequentially through a peristaltic pump at 5-min collection intervals for 2 h. Sequential plasma samples were assayed for LH by RIA. Pulse analysis was performed using PC PULSAR [ 15]. No significant differences in pulse frequency or amplitude were found between CR and UR either at day 6 or 12. However, the number of animals exhibiting detectable pulses was reduced in UR when compared to CR. At 12 days after OVX, 100% of CR showed detectable pulses at all doses of E₂, while 100, 60, 50 and 17% of UR had detectable pulses at 0, 1.2, 2.4 and 4.8 µg doses of E₂, respectively. UR with detectable pulses had mean LH concentrations which did not differ from those of CR, but UR which no longer exhibited detectable pulses had mean LH concentrations significantly lower than CR. These results suggest that the suppression of LH pulses by E₂ in UR may be an ‘all-or-none’ phenomenon, more likely to occur at a hypothalamic (or other CNS) site than at the pituitary level.

Estrogen feedback needed at the paraventricular nucleus or A2 to suppress pulsatile luteinizing hormone release in fasting female rats.

“…Previous studies (6,24) demonstrated that the greater the E2 dose to OVX rats, the greater the suppression of pulsatile LH secretion during fasting. This implies a negative feedback effect of estrogen, which tonically suppresses LHRH or LH release in intact animals.…”

Increase in daily LH secretion in response to short-term calorie restriction in obese women with PCOS

“…In the sheep (6,45), rat (28,41), hamster (5,24,37), and monkey (14), the latter change reduced GnRH-dependent LH pulsatility. Insulin concentrations also fell (see below), as expected, in response to caloric deficiency.…”

“…mammalian species (55). Several endocrine and metabolic cues that are affected by caloric intake (i.e., glucose, leptin, insulin, and steroid hormones) are known to modulate LH secretion (1,15,41,42). Also, calorie restriction seems to enhance the negative feedback actions of estradiol on pulsatile GnRH and LH secretion (30,41), possibly by altering estrogen receptivity in the hypothalamus (24).…”

The female reproductive axis and its modifications during the post-partum period

“…Return of menses has been observed in patients with primary hypothalamic amenorrhoea treated with naltrexone over an extended period of time (Wildt & Leyendecker, 1987), although the protocol and the small number of cases limit the conclusions. In rats naloxone could prevent the effect of starvation on the oestradiol-induced central nervous system effects (Spillar & Piacsek, 1991). Although the detailed mechanism of opiate action is not known, rat studies suggest the involvement of the morphin ^-receptors (/i-R) (Dyer et ai, 1985;Martini et al, 1989).…”

“…Recent studies have yielded new information. Spillar & Piacsek (1991) studied 45day-old female rats randomly assigned to a control or a moderately underfed group. After 12 days no more pulses could be observed in the underfed group, while LH pulses depended on the oestradiol level in the control group.…”