Persistence of Diurnal Periodicity of CRF Activity in Adrenalectomized and Hypophysectomized Rats

Takebe, Kazuo; Sakakura, Muneki; Horiuchi, Yoshihiko; Mashimo, Keimei

doi:10.1507/endocrj1954.18.451

Cited by 5 publications

(1 citation statement)

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“…er apparently drives the rhythm of hypothalamic corticotropin-releasing factor (CRF) content (5), which presumably leads to a daily periodicity in adrenocorticotropic hormone (ACTH) production by the anterior pituitary, and the selfsustained adrenal rhythm is entrained by the oscillating plasma ACTH concentration (3). Richter (2) suggested that the circadian clock would be located somewhere in the hypothalamus of the brain.…”

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An effect of castration and testosterone replacement on a circadian pacemaker in mice (Mus musculus).

Daan

Damassa²,

Pittendrigh³

et al. 1975

Proc. Natl. Acad. Sci. U.S.A.

172

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Castration of mice in freerunning conditions (total darkness, DD) causes a reduction of running wheel activity in the beginning of the active period (a) and stimulates activity at the end of a. Simultaneously, the period (r) of the freerunning rhythm is increased. Both effects are abolished by implantation of a Silastic capsule from which a physiological dose of testosterone is released at a constant rate. The results are tentatively explained by differential endocrine influences on two oscillating components in the pacemaker of the circadian activity rhythm. Early work on endocrine involvement in circadian rhythms was mainly aimed at the localization of the clock within the various endocrine glands or within a cycle of nervous-endocrine-metabolic events (1). Much of the research was done in animals exposed to daily light-dark cycles, which precludes evidence on the endogenous nature of the rhythmic phenomena observed. From a series of experiments on blinded rats, Richter (2) stated that freerunning circadian activity rhythms were not impaired by any of the following interferences with the endocrine system: gonadectomy, adrenalectomy, hypophysectomy, hyper-or hypothyroidism, and pinealectomy. Apparently, the circadian clock driving the activity-rest cycle was not located in any of the glands involved. The demonstration by Andrews (3) that rat adrenals cultured in vitro continue to produce corticosteroids in a circadian rhythmic fashion considerably modified existing views in the field concerning the regulating function of a localized clock (4). Evidently, since at least one organ, and probably more, is capable of self-sustained oscillations, a centralized "clock" or "pacemaker" would serve to synchronize a number of peripheral oscillators rather than impose its rhythm on them. For instance, a circadian pacemaker apparently drives the rhythm of hypothalamic corticotropin-releasing factor (CRF) content (5), which presumably leads to a daily periodicity in adrenocorticotropic hormone (ACTH) production by the anterior pituitary, and the selfsustained adrenal rhythm is entrained by the oscillating plasma ACTH concentration (3). Richter (2) suggested that the circadian clock would be located somewhere in the hypothalamus of the brain. There is now evidence (6) (9) show that pharmacological doses of testosterone can cause a severe disruption ("splitting") of the circadian activity rhythm in starlings. This led us to reinvestigate the effects of gonadectomy and subsequent testosterone replacement on a mammalian circadian rhythm, as a first approach to the questions of peripheral feedback. MATERIALS AND METHODSTwelve mice (Mus musculus C57BI/6S), born March 12-14, 1974, were obtained from Simonson Laboratories (Gilroy, Calif.) and housed individually in wire mesh cages (23 X 19 X 33 cm), each in a ventilated light-tight box. The cages were equipped with running wheels, and an Esterline-Angus event recorder was used to monitor wheel revolutions. The animals were kept in constant darkness (DD) for the duration of t...

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