Neonatal Ablation of the Suprachiasmatic Nucleus. Effects on the Development of the Pituitary-Gonadal Axis in the Female Rat

Abstract

Ablation of the suprachiasmatic nucleus (SCN) at 2 days of age, prior to the formation of the retinohypothalamic projection, produces a permanent state of constant vaginal estrus in the postpubertal female rat. Although such lesions do not alter the onset of puberty in sighted rats, they do compensate for the delay in vaginal opening induced by neonatal blinding. The ovaries of sighted and blinded SCN-lesion rats are small and polyfoUicular and the pituitaries of blinded SCN-lesion rats are abnormally large. Sampling of plasma in the morning and afternoon for up to 12 consecutive days in sighted SCN-lesion rats reveals continuously low luteinizing hormone levels. This constellation of endocrine alterations does not correlate with damage to any structures outside the SCN. Since the organization of the rodent estrous cycle is circadian, these results emphasize further the importance of the SCN in circadian rhythm generation. The necessity of an intact SCN for the development of normal, cyclic reproductive function implies that sparing or recovery of function does not occur.

Biological rhythms and fertility: the hypothalamus–pituitary–ovary axis

“…28,59 Disruption of biological rhythms across the HPO axis: animal studies Several pioneer studies have shown that SCN ablation or lesions in rats result in irregular estrous cycles and the inhi bition of LH surge and of ovulation. 23,60,61 These results have been confirmed by recent studies of core clock gene mutants and mutant cell lines.…”

Disruption of circadian regulation by brain grafts that overexpress Alzheimer beta/A4 amyloid.

“…The SCN oscillator function is robust and is moderately resistant to mechanical damage (19,20 (25,26). The biological activity of f3/A4 and homologous peptides has been observed in several experimental systems (27)(28)(29).…”

The Interplay between Circadian System, Cholesterol Synthesis, and Steroidogenesis Affects Various Aspects of Female Reproduction

“…The administration of barbiturates that prevent signaling within the SCN to rats prior to this event blocks the LH surge and ovulation and delays them for 24 h (3). Additionally, studies on SCN lesions in rats resulted in the absence of ovulation (46, 47). Combined, these studies provide evidence that a signal from the circadian system is crucial for successful ovulation.…”