Action of Adrenocorticotropin on Pregnancy and Litter Size in Rats

Abstract

Previously it was reported that adrenocorticotropin (ACTH) displayed the ability to restrict the action of estradiol-17ß in uterine growth and of progesterone in decidual development. This study concerns the influence of a highly purified and potent preparation of ACTH on pregnancy and litter size in albino rats of known reproductive vigor. Experimental procedures consisted of injecting ACTH prior to, immediately after mating and 11 days after mating. These data indicate that ACTH has the ability to reduce litter size and produce a large number of stillbirths. The most marked effects were observed when ACTH was injected on the day of mating and for 6 subsequent days. Normally, the litter size of nontreated controls is 9.6 ± 0.5. The daily injection of 2.0 and 4.0 mg ACTH daily for 7 days after mating effected reduced litters, 5.0 ± 1.7 and 3.9 ± 1.5, respectively. Furthermore, such treatment produced 27 stillborns on the 2.0-mg dosage and 39 on the 4.0-mg treatment. ACTH administered to adrenalectomized rats neither modified pregnancy nor litter size. ACTH given to intact rats effected a decrease in the fetal body weights. Such was not observed in the adrenalectomized groups nor in the ACTH-treated, adrenalectomized series. These data strongly indicate that the effects observed are mediated by way of the adrenal glands, and additional evidence is offered supporting the contention that there are numerous interactions among hormones of adrenal cortex and the ovaries.

Effect of the long-term administration of corticotropin-releasing factor on the pituitary-adrenal and pituitary-gonadal axis in the male rat.

“…Some investigators have suggested that stress-induced increased levels of circulating corticosteroids and/or adrenal androgens would decrease pituitary responsiveness to GnRH, and therefore LH secretion (32)(33)(34)(35)(36), or exert a direct inhibitory action on steroidogenesis (31, 33, 37, 38). Others have reported that ACTH, but not corticosterone, could delay puberty (39), interrupt pregnancy (40)(41)(42), and inhibit ovulation (43). We have recently observed that the intracerebroventricular administration of CRF markedly lowered LH secretion in gonadectomized/ adrenalectomized rats, while acutely large doses of peripherally administered CRF were without effect (13).…”

The effect of restraint stress in early pregnancy in mice

“…Restraint is an effective means of activat¬ ing the hypothalamic-pituitary-adrenal axis (Riegle, 1973) and the specific Stressor used in this study (restraint in a wire-mesh cone) has been shown to raise plasma corticosterone concentrations (and presumably ACTH) 3-fold over those in control mice (Blecha et al, 1982). Both ACTH and adrenal corticoids have been shown to affect pregnant laboratory rodents (Velardo, 1957;Kittinger et al, 1980). Since both hormones show a circadian rhythm in mice and rats (Guillemin, Dear & Liebelt, 1959;Halberg, Peterson & Silber, 1959;Retienne, Zimmermann, Schindler & Lipscomb, 1968) with blood levels peaking before the onset of darkness, it would not be unexpected to see responses to stress varying at different times of the day.…”

“…Auditory stimuli at regular intervals for 48 h appeared to interfere with the implantation process in rats (Zondek & Tamari, 1967), but the exact stage of pregnancy at the time of stimulation was not known. Administration of adrenocorticotrophic hormone (ACTH) on the day of mating and for 6 subsequent days reduced the litter size in rats and this effect appeared to be mediated through the adrenal glands (Velardo, 1957). In contrast, Kittinger, Gutierrez-Cernosek, Cernosek & Pasley (1980) reported that ACTH treatment for the first 8 days of pregnancy reduced the number of implantation sites in intact and adrenalectomized mice.…”

Different mechanisms for the inhibition of progesterone secretion by ACTH and corticosterone in pregnant rats

“…The stress of restraint during early pregnancy decreases the average size of litters in rats (Euker & Riegle, 1973;Herrenkohl, 1979;Wiebold, Stanfield, Becker & Hillers, 1986) and serum progesterone concentrations in mice (Wiebold et al 1986). Involvement of the pituitary-adrenal axis in the maintenance of preg¬ nancy has also been demonstrated in several species (Velardo, 1957;Yang, Yang & Lin, 1969;Christian, 1971;Kittinger, Gutierrez-Cernosek, Cernosek & Pasley, 1980;Rosa & Wagner, 1981;Hellar & de Nicola, 1983). Recently, Kato, Nanjo, Numa et al (1988) demonstrated that adrenocorticotrophin (ACTH) and corticosterone inhibit progesterone secretion during mid-pregnancy in rats.…”