Effects of Discrete Lesions of Preoptic and Suprachiasmatic Structures in the Female Rat

Abstract

The purpose of this study was to determine which specific structures within the medial preoptic-anterior hypothalamic area are necessary to maintain cyclic ovulation in the rat, and to define the deficit(s) in the feedback regulation of gonadotropin secretion associated with lesions that result in anovulation. Large (∼1.1 mm dia.) or small (∼0.7 mm dia.) electrolytic lesions were placed in several loci within preoptic, anterior hypothalamic and suprachiasmatic areas in regularly cycling adult female rats. Large lesions which included the suprachiasmatic nuclei (SCN) induced an anovulatory condition characterized by persistent vaginal cornification and polyfollicular ovaries (persistent estrus). Large or small lesions which included the medial preoptic nucleus (MPN), a small periventricular column of cells located immediately caudal to the organum vasculosum of the lamina terminalis (OVLT), also induced persistent estrus. Lesions placed elsewhere within the medial preoptic-anterior hypothalamic area never induced persistent estrus but were frequently associated with repeated periods of prolonged diestrus separated by brief periods of vaginal cornification. These prolonged diestrous intervals appeared to be related to spontaneous luteal activation following ovulation rather than impaired folliculogenesis. LH and FSH surges induced by sequential administration of estradiol benzoate and progesterone (P) were completely abolished only by lesions which included the MPN. Small lesions involving only the MPN and OVLT or the MPN and caudally adjacent loci in the suprachiasmatic region were as effective in this respect as larger lesions encompassing most of the preoptic-suprachiasmatic region from the diagonal band of Broca to the rostral pole of the SCN. On the other hand, P-induced gonadotropin surges were never completely blocked by SCN lesions, although the magnitude of the surge was highly variable and frequently attenuated compared to controls. It is concluded that both the MPN and SCN are required for the long-term maintenance of spontaneous cyclic ovulation in the rat. However, the characteristically dissimilar deficits in P-induced gonadotropin release associated with lesions of one or the other of these structures indicate that these nuclei may play different roles in the regulation of gonadotropin surges. It is suggested that neural elements indispensable for phasic gonadotropin release are located within and/or immediately adjacent to the MPN. The SCN may influence phasic gonadotropin release indirectly, by regulating circadian rhythms which govern the responsiveness of other neural elements to hormonal stimuli.

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.…”

“…In other words, the timing of the LH surge, and therefore the timing of ovulation, is highly determined. 23,24 As for other seasonal and circadian rhythms, the timing of reproductive function in mammals, including humans, is also orchestrated mainly by the SCN as part of the hypothalamuspituitary-ovary (HPO) axis. The functioning of the HPO axis is a good example of the tight interconnections and circadian synchronization between neural, endocrine, and neuro endocrine signals that result in the ovarian cycle, ie, the main component of reproduction in female mammals.…”

Kiss1 Neurons in the Forebrain as Central Processors for Generating the Preovulatory Luteinizing Hormone Surge

“…Second, there is compelling evidence that the GnRH/LH surge is generated by E-sensitive neurons whose cell bodies reside in the AVPV and are activated by a circadian signal from the suprachiasmatic nucleus (SCN) (Gu and Simerly, 1997;de la Iglesia and Schwartz, 2006). Lesions of the AVPV block spontaneous and steroidinduced LH surges (Wiegand et al, 1978(Wiegand et al, , 1980Terasawa et al, 1980;Wiegand and Terasawa, 1982;Ronnekleiv and Kelly, 1986;Ronnekleiv and Kelly, 1988;Le et al, 1999). Third, the AVPV is sexually differentiated, with females having greater numbers of cells than males (Simerly, 1998), and the surge mechanism is only present in the female rodents (Pfeiffer, 1936;Barraclough, 1961;Gogan et al, 1980;Corbier, 1985;Hoffman et al, 2005).…”

A genetically female brain is required for a regular reproductive cycle in chicken brain chimeras

“…Timed preovulatory activation of GnRH neurons depends mainly on two factors: a rising concentration of E2 during the follicular phase of the oestrous cycle and a circadian timekeeping system. The master circadian pacemaker in mammals is located in the suprachiasmatic nuclei (SCN) of the hypothalamus, and classic experiments have shown that surgical ablation of SCN results in disruption of the oestrous cycle in rats 33,34 . Mutations in key circadian rhythm genes such as Clock or Bmal1 in mice affect female reproductive function resulting in an extended and irregular oestrous cycle 35,36 .…”