Sex Differences in the Daily Rhythm of Vasoactive Intestinal Polypeptide But Not Arginine Vasopressin Messenger Ribonucleic Acid in the Suprachiasmatic Nuclei¹

Abstract

The timing of the preovulatory surge of LH in female rodents is tightly coupled to the environmental light/dark cycle. This coupling is mediated by the circadian pacemaker located in the suprachiasmatic nuclei (SCN). Studies indicate that vasoactive intestinal polypeptide (VIP) and arginine vasopressin (AVP), which are synthesized in the SCN, transmit circadian information from the SCN to GnRH neurons, thereby regulating the timing of the LH surge. However, to date, the rhythmic expression of these two peptides in the SCN has only been examined in males. The pattern of VIP expression in males is difficult to reconcile with its role in the LH surge. The purpose of the present study was to assess the rhythm of VIP messenger RNA (mRNA) levels in the SCN of female rats under several endocrine conditions. We compared this rhythm to that in males and to AVP mRNA rhythms in all experimental groups. In all groups of females, VIP mRNA levels were rhythmic, with peak expression occurring during the light phase and a nadir occurring during the dark phase. The rhythm was approximately 12 h out of phase compared with that in males. The rhythmic expression of AVP mRNA in the SCN was virtually identical in all groups of animals. Based on these results, we conclude that 1) the rhythm of VIP seen in the SCN of females during the day may serve as a facilitory signal from the SCN to GnRH neurons; 2) the sex-specific pattern of VIP mRNA does not depend on estradiol; and 3) AVP gene expression within the SCN is not sexually differentiated or altered by estradiol. (Endocrinology 139: 4189 -4196, 1998) T HE SYNCHRONIZATION of numerous neurochemical and hormonal events is necessary for ovulation and the induction of behavioral receptivity in many female species. In rodents, these physiological events are tightly coupled to the environmental light/dark (LD) cycle, so that when circulating estrogen levels are high, such as on the day of proestrus, an ovulatory surge of LH occurs at a very specific time in relationship to the LD cycle (1, 2). The timing of behavioral receptivity also is tightly coupled to the LD cycle in female rodents and occurs only at a specific time on the evening of proestrus (3). Synchronization of ovulation and behavior is important for maximizing reproductive success.Numerous studies have demonstrated that a circadian pacemaker controls the timing of the LH surge (4) and receptive behavior (3), and insures that these rhythms are tightly coupled to the environmental LD cycle. First, treatment with pentobarbital on the morning of proestrus blocks the preovulatory surge of LH. However, a LH surge occurs at the predicted time on the following day, indicating that a daily neurochemical signal is responsible for generating LH surges (5). Second, female rodents housed in LD cycles of varying lengths (i.e. 21-24 h) vary the lengths of their reproductive cycle, such that a single estrous cycle is exactly 4 times the length of the LD cycle to which the animals are exposed (6). Furthermore, animals housed in the a...

Neuroendocrine mechanisms underlying estrogen positive feedback and the LH surge

“…In female mice, more kisspeptin neurons show AVP appositions with E 2 treatment (Vida et al, 2010); by contrast, in the same animals, VIP connections to RP3V KISS neurons were reported to be far less prevalent, regardless of E 2 treatment (Vida et al, 2010). Supporting this anatomical data are correlational findings that SCN AVP levels are circadian, peaking in the late subjective day similar to circadian increases in RP3V KISS neurons and the LH surge (Reppert et al, 1981;Krajnak et al, 1998), and E 2 increases V1a levels in the POA area (which contains the RP3V; Funabashi et al, 2000;Kalamatianos et al, 2004).…”

Functional Implications of RFRP-3 in the Central Control of Daily and Seasonal Rhythms in Reproduction

“…AVP release in the SCN vicinity has been found to peak during midday while minimum release occurs at midnight (90). Unlike VIP, no sex-dependent differences in AVP gene expression are found in the SCN (80). Increasing evidence indicates that the rhythm in SCN AVP release is critical for the daily timing of the preovulatory LH surge.…”

“…VIP content in the rat SCN displays daily variation which is abolished under constant darkness, suggesting that VIP is implicated in the transmission of photic information (79). Furthermore, the daily rhythm in SCN VIP appears sex-dependent since VIP mRNA levels peak during the light phase in female rats but during the dark phase in male rats (80). The observation that a central blockade of VIP signaling decreases the LH surge in female rats indicates a role of this peptide in female reproduction (81, 82).…”

Estradiol Regulates Circadian Responses to Acute and Constant Light Exposure in Female Mice

“…For example, castration in males reduces the number of photic-induced c-fos neurons within the SCN (Karatsoreos et al, 2007), but OVX in females (Brockman et al, 2011) or ER KO (Blattner and Mahoney, 2013) does not affect photic-induced c-fos expression (c-fos being a marker for photic inputs to the SCN). In addition, OVX does not significantly change vasoactive intestinal polypeptide (VIP) levels within the SCN of female rodents nor does estradiol application modify vasoactive intestinal polypeptide (VIP) signaling in LD (Krajnak et al, 1998). Future studies connecting estrogen signaling and photic inputs to the circadian timing system would be of great interest to determine why depleted estrogen signaling affects responses to light exposure.…”