The reproductive system exhibits various rhythmic cycles over time. There is a diurnal cycle that is regulated by the interaction of intrinsic timing mechanisms and entrainment by cycles of day and night. There is also an estrous cycle of spontaneous ovulation in many muroid rodents. Of longer duration are annual cycles of reproductive fertility, which may also represent an internal rhythm entrained by seasonal stimuli. Finally, there are irregular cycles of fertility by individual animals and sometimes by entire populations that are influenced by social factors such as overcrowding.
Two of the longer cycles of reproduction have certain features in common which suggest that they may both involve an active suppression of the pituitary-gonadal system. In trying to explain this phenomenon, I have found it useful to postulate that it is caused by the activation of an "
In the case of the suppression of reproduction which occurs during overcrowding and fighting in muroid rodents, there is evidence to suggest that the sequence of CRF-ACTH-adrenal corticosteroid production by the pituitary-adrenal axis :functions as part of an "anti-gonad system."
Adrenocortical activity is stimulated by defeat in mice, and, subsequently, by the stimuli associated with that defeat (Bronson and Eleftheriou, 1964). As mentioned earlier, this effect may be understood in terms of CRF secretion as a motor pattern of submission. This process is not confined to laboratory conditions; Christian (1975) has amassed a large amount of data from many species of muroid rodents showing that there is a correlation between hypertrophy and hyperactivity of the pituitary-adrenal axis and overcrowding. There are also data to indicate that pituitary-adrenal hormones can suppress reproductive function.
As mentioned earlier (site 13), ACTH has been shown to block LRF and LH secretion under experimental conditions (Ogle, 1977). Also, high levels of ACTH have been shown to block normal gonadal maturation in mice (Christian and Davis, 1964; Jarret, 1965). Some of the effect of ACTH may be due to its facilitation oŁ adrenal production oŁ progestins that block gonadotropin secretion, but, in addition, there must be a direct effect on the pituitary since the effect has been reported in mice after removal of the adrenals (Christian, 1964). This process, also, is not confined to special laboratory conditions. After crowding or repeated defeats, the secondary sexual characteristics of rats, mice, golden hamsters and Mongolian gerbils become atrophied, apparently due to declining levels of gonadal hormones (Christian, 1961; Bronson and Eleftheriou, 1964; Chapman et al, Thiessen et al, 1970a; Lloyd, 1971; Bronson and Marsden, 1973). One recent study failed to find such consistent effects, however, in laborstory mice (Selmanoff et a1, 1977).
So far, the data on the pituitary adrenal system as an "anti-gonad" is only correlational rather than causal. As far as I know, it has not been shown that the pituitary-adrenal system is necessary for the suppression of gonadal function by overcrowding and defeat. Such a demonstration might take the following form. One would expect that an adrenalectomized animal, maintained on constant levels of replacement corticosteroids, should have no suppression of gonadal function following defeat. Alternatively, if ACTH levels were critical, one would expect that an animal with ACTH secretion suppressed, e.g. by dexamethasone implants in the hypothalamus, should have no suppression of gonadal function following defeat and overcrowding,
One phenomenon combines features of both overcrowding and seasonal suppression of gonadal function. This phenomenon consists of a postonement of gonadal maturity by juveniles born late in the season so that puberty occurs in the following spring. It is found in many species of muroid rodents under natural conditions (Schwarz et al, 1964; Krebs, 1964; Christian, 1971). Analogous effects have been obtained in laboratory studies in which gonadal maturity is postponed if a litter is kept with its parents and littermates; this has been shown in both voles (Batzli et al, 1977) and gerbils (Swanson and Lockley, 1978). It has been suggested that the effect is mediated by pituitary-adrenal responses to the overt fighting and defeat which occurs during the overpopulation late in the reproductive season (Rowley and Christian, 1977), or that it may be mediated by olfactory stimulation without any fighting being necessary (Batzli et a1, 1977). Again, however, direct data have not yet been obtained to show unequivocally that the pituitary-adrenal axis is necessary for this postponement of gonadal maturity.
One might expect that the pituitary-adrenal system was also responsible for the gonadal suppression that occurs during the winter in most muroid rodents. Correlational evidence is available, as many muroid rodents have been found to have hypertrophied adrenal glands during the winter (Negus et a1, 1961; Schwarz et a1, 1964; Andrews et al, 1972: Since cold stress can produce pituitary-adrenal activity in laboratory experiments, this may be one mechanism of the "wintering'. effect.
Gonadal suppression during the winter may also be triggered by the shortening photoperiod (i.e. shorter days) that precede the winter. Laboratory hamsters (Elliott et al, 1972) and voles (Grocock and Clarke, 1974), kept under controlled conditions, show gonadal regression after prolonged exposure to short photoperiods. This process depends upon a complex and still undeciphered relationship among the rhythmic activities of the pineal gland (Reiter, 1973), its hormone melatonin (Goldman et al, 1979), the suprachiasmatic nucleus of the hypothalamus (Morin et a1, 1977), and probably other structures and hormones as well. The role played by the pituitary-adrenal axis in this process has not yet been determined. In one relevant study, the weight of the adrenals was slightly enlarged in hamsters after pinealectomy and was diminished in sham-operated animals when exposed to short photoperiods although these effects were not statistically significant, and direct measures of adrenal function were not made (Hoffman and Reiter, 1966). Another recent study examined the effects of adrenalectomy upon hamsters exposed to short photoperiods, but the study was marred by deaths of many adrenalectomized animals; perhaps as a result, there were no statistically significant differences found in the gonadal regression between groups exposed to long and short photoperiods (Bittman and Zucker, 1977).
In summary, one may suppose that there may be an "anti-gonad system" in muroid rodents. The pituitary-adrenal system plays an active role, at least in the responses to overcrowding and fighting, although other neural or endocrine structures may play critical roles as well. The mechanisms of anti-gonadal activity in response to seasonal stimuli are less clear, and certainly involve other mechanisms besides or instead of the pituitary-adrenal axis. Hopefully, more data will become available in future experiments to define the system more precisely.