Photoresponsive Fischer 344 Rats are Reproductively Inhibited by Melatonin and Differ in 2‐[¹²⁵I] Iodomelatonin Binding from Nonphotoresponsive Sprague‐Dawley Rats

Abstract

Many temperate-zone species use photoperiod as an environmental cue to regulate reproductive timing. Strains of laboratory rats differ in their responsiveness to photoperiod, with the Fischer 344 (F344) strain being the most responsive known. F344 rats and closely related strains that differ in photoresponsiveness may be useful models to study the mechanisms and genetic basis for photoresponsiveness. We tested two hypotheses: (i) that melatonin mediates photoresponsiveness in F344 rats, as is the case in all other mammals tested, and (ii) that the location, abundance, or affinity of melatonin receptors, as estimated by the amount and location of binding of the radioligand 2-[125I]-iodomelatonin (IMEL) in the brain, might cause variation in photoresponsiveness among rat strains. Melatonin injections 1 h before lights off in a stimulatory photoperiod (L14 : D10) induced reproductive inhibition and reduced weight gain in a manner similar to short days of L8 : D16, while injections of ethanolic saline vehicle did not. Interestingly, melatonin injections administered during an inhibitory photoperiod (L10 : D14) caused greater inhibition of both reproduction and weight gain than short photoperiod alone. Pinealectomized F344 rats implanted subcutaneously with melatonin in a silastic capsule did not differ in testis size or body weight from controls with blank implants. The brains and pars tuberalis of the pituitary from photoresponsive F344 rats and nonphotoresponsive Harlan Sprague-Dawley (HSD) rats were processed for autoradiography using IMEL. We found significantly higher specific IMEL binding in the anterior and posterior regions of the paraventricular nucleus of the thalamus (PVNt) and reuniens nucleus of the thalamus of F344 rats than in the same areas in HSD rats. There were no differences between strains in specific IMEL binding in the medial PVNt, anteroventral and anterodorsal nucleus of the thalamus, suprachiasmatic nucleus, or the pars tuberalis. These results indicate that melatonin mediates photoresponsiveness in F344 rats. In addition, they provide support for the hypothesis that F344 rats may be photoresponsive due to differences from other strains in the location, density, or affinity of melatonin receptors.

Differential response of type 2 deiodinase gene expression to photoperiod between photoperiodic Fischer 344 and nonphotoperiodic Wistar rats

“…1). This result was consistent with previous reports that the Wistar strain is a reproductively nonphotoperiodic strain, while the F344 strain is sensitive to photoperiod (11,12,14,17,28).…”

“…Testicular volume was also suppressed in both strains, although a slight individual variation was observed in the Wistar rats (data not shown). Previous research has also demonstrated that daily melatonin injections in the late afternoon under long days or under a 12:12-h light-dark cycle inhibit testicular development in F344 rats (12) and young Wistar rats (30). These results suggest that both strains are capable of responding to melatonin.…”

“…Since daily melatonin injections during late afternoon suppress Dio2 expression in the MBH of Djungarian and Syrian hamsters (29, 37), we next examined the effect of daily melatonin injections on Dio2 expression in F344 and Wistar strains under long-day conditions. This experimental design is known to mimic the short-day effect on gonadal growth in the Syrian hamster (32), the Djungarian hamster (31), and the F344 rat (12). As a result, Dio2 expression in the TIS and EC was suppressed in both F344 (Mann-Whitney U-test, P Ͻ 0.01) and Wistar (Mann-Whitney U-test, P Ͻ 0.01) strains (Fig.…”

“…In contrast, the Fischer 344 (F344) inbred strain of rat exhibits robust photoresponsiveness, even under normal conditions, exhibiting slower gonadal growth on exposure to short days (11,14). Gonadal development of F344 rats is also inhibited by blinding (17) or by melatonin injection (12). A recent study has also reported that the ACI, PVG, and BUF inbred rat strains are also photoperiod sensitive (6), suggesting that sensitivity to photoperiod varies across different rat strains.…”

Failure to respond to endogenous or exogenous melatonin may cause nonphotoresponsiveness in Harlan Sprague Dawley rats

“…We chose these two strains because young F344 rats have the greatest response to short photoperiod reported in rats, and HSD rats are the only strain for which there is clear evidence for a lack of response to short photoperiod [21,23,27]. In order to further examine the effects of photoperiod on melatonin, the question of whether young HSD rats would exhibit inhibition of reproductive development in response to constant dark or supplemental timed injections of melatonin was tested.…”