Karmela Milković

Reactiveness of fetal pituitary to stressful stimuli. Does the maternal ACTH cross the placenta

Summary Stressful stimulus in intact fetuses, but not in decapitated fetuses, caused adrenal ascorbic acid depletion. ACTH injection into decapitated fetuses was followed by considerable adrenal ascorbic acid depletion. These data support the concept that the placenta is not permeable to ACTH.

Development of steroidogenesis in the fetal rat adrenal gland: An in vitro study ☆

Abstract In vitro synthesis of steroid hormones from [4-14C]-progesterone by the adrenal glands of rat fetuses with various pituitary adrenocorticotropic activities has been investigated. The fetal adrenal glands are capable of synthesizing deoxycorticosterone, corticosterone, 18-hydroxy-11-deoxycorticosterone, 18-hydroxy-corticosterone, 11-dehydrocorticosterone and aldosterone. Adrenal corticosterone synthesis begins on the 14th day of fetal life and continues uninterrupted until delivery. On the 18th day corticosterone synthesis sharply increases, because of the activation of fetal ACTH which induces quantitative changes in fetal steroidogenesis. The yield of radioactive conversion products per unit of fetal adrenal weight decreases during the intrauterine development. The biotransformation of hormones per unit of gland weight depends on the age of fetuses and not on the degree of fetal adrenocorticotropic activity.

Progeny of male rats treated with methadone: physiological and behavioural effects.

Male rats were injected with methadone HCl (METH) at 5 mg/kg s.c. for 4 days prior to mating with drug-free females. Offspring resulting from these matings were compared with offspring of drug-free males. The progeny of METH-treated males gained less weight after weaning and had lighter thymuses as adults (but not in infancy). Gonadal weights did not differ in infancy or adulthood, and adrenal weights were heavier in female offspring in adulthood. In adulthood METH offspring were significantly different from controls on all behavioural tests used (open field activity, activity cage activity, passive avoidance latencies, shuttle box avoidances, and rotarod latencies), with the differences frequently affected by test order, days of testing, or sex of offspring. The effects in progeny of METH-treated males in the absence of differences in litter size or neonatal mortality indicate that paternal drug ingestion prior to mating can produce physiological and behavioural changes in progeny that are not dependent on detectable effects on early viability or growth.

Reproductive ability of pubertal male and female rats

Ten Fisher rats 50 to 55 days of age made up the pubertal group, and ten rats 90 to 95 days of age served as the controls. The testicular and epididymal weights and volumes of the pubertal males were lower than those of the controls (P<0.001). There was also a difference in relative epididymal weight (P<0.001). The sperm of pubertal males was morphologically abnormal in 58.2% of cases, as opposed to only 3.8% in the controls (P<0.001). The mean number of spermatozoa in the control group was 11.9 10(6)/ml and their viability was 99.6%, while these values could not be determined for pubertal rats. Serum testosterone was higher in the pubertal animals than in the controls (2.52 1.46 vs 0.92 0.34 nM, P<0.01). The ovaries of control females were heavier than those of pubertal females (P<0.001) but there was no difference in their relative weights. Serum estradiol was similar in both groups (75.5 12.8 vs 81.8 14.7 nM, P>0.05). At the beginning of gestation, the pubertal dams weighed less than the controls (P<0.001) but following uterectomy the body weights were equal. Pubertal dams delivered fewer pups than the controls (8.1 2.5 vs 10.4 1.3, P<0.05). There was no difference in the body weights of their offspring or in the weights of their placentas. The results suggest that, in contrast to their female counterparts, pubertal male rats are not fully mature and have not reached complete reproductive capacity at 50-55 days of age.

Feedback Control of Pituitary—Adrenal Activity in Fetus

Publisher Summary This chapter discusses the dependence of growth and functional differentiation of fetal adrenal glands on the weight and secretory activity of the mothers adrenal glands as well as the results of an attempt to determine the quantitative participation of the fetal pituitary in the growth of the fetal adrenal glands. In a study described in the chapter, during the second week of gestation, adrenal weight of the tumor-bearing pregnant rat increased by 52%, and the thymus weight decreased slightly (30%). The last week was characterized by almost four times enlargement of the maternal adrenal glands and a very pronounced thymolytic effect. Adrenal weights of the fetuses increased from the 17th to 21st day of intrauterine development from 0.24 mg to 1.77 mg and were somewhat lighter on the last day (1.70 mg). Adrenal weights of the fetuses from an adrenocorticotropic hormone (ACTH)-secreting tumor-bearing mother also increased, but only from 0.22 mg to 0.64 mg from day 17 to day 21, and 0.76 on the last day of pregnancy. The average daily increase of fetal adrenal weight in mothers with enlarged adrenals was 0.11 mg, which is less than 30% of the daily adrenal weight gain of the control fetuses.

Differential Effect of Pre- and Postnatal Litter Size Reduction on Body Weight and Development of Stress Response in the Rat

The postnatal development of pups belonging to the small, prenatally reduced litters (PRN) was compared to that of pups of the postnatally reduced litters (PST) and to that of pups of intact, normal-size litters (CON). Body adrenal and pituitary weight gain as well as maturation of the pituitary-adrenal system were enhanced in the PRN and PST pups as compared to the CON pups in the 3 postnatal weeks. However, significant differences in some data between the PRN and PST pups were found, indicating the more pronounced beneficial effect of the prenatal reduction of litter size. The postnatal litter size reduction abolished the weight gain of the testes. The prenatal reduction of litter size resulted in a similar, although less pronounced negative effect.

Behavioral characteristics of the offspring of adolescent rats

The aim of this study was to test the hypothesis that, during adulthood, the offspring of adolescent rats differ in emotionality, learning and memory from the offspring of adult rats. The behavior of the offspring of adolescent (age, 50-55 days) and adult rats (age, 90-95 days) was tested in the open field, activity cage, and passive and active avoidance apparatus. The latencies during training and testing in the passive avoidance apparatus of the offspring of adolescent parents were shorter than the latencies of control offspring (P<0.001 on both training and testing days). Offspring of adolescent parents showed shorter latency time in acquisition trials during active avoidance testing compared to control offspring (P<0.001). They also showed a higher number of active avoidance responses in the last four blocks of acquisition (P<0.001) and first two blocks of extinction trials (P<0.05 and P<0.001, respectively). The offspring of adolescent parents showed higher latency on the first day of testing in the open field (P<0.01) and a lower latency on the third day of testing (P<0.01). They also showed higher activity during all three days of testing (1st and 2nd day: P<0.01; 3rd day: P<0.05). The spontaneous activity of the offspring of adolescent parents in the activity cage was higher in the last three intervals of testing (P<0.001). In summary, the offspring of adolescent parents were less anxious and tended to be more active. The results of two learning and memory tests were opposite, but could be explained by a higher exploratory drive of the offspring of adolescent parents. This was probably due to chronic malnutrition stress and the disturbed mother-infant relationship in the litters of adolescent mothers.

Steroidogenesis of the fetal adrenal gland in vitro: influence of metopirone applied in vivo and in vitro.

Summary In vitro conversion of 4-14C-progesterone into corticosteroids in the adrenal glands of rat fetuses treated with Metopirone (Su 4885) on the last day of intrauterine development was studied. After a 1-hr incubation of the adrenal glands of fetuses injected with Metopirone, hydroxylation of progesterone into corticosterone (B), 18-hydroxycorticosterone (18-OH-B) and 18-hydroxy-11-deoxycorticosterone (18-OH-DOC) decreased and the synthesis of 11-deoxycorticosterone increased. Following preincubation of the fetal adrenal glands and 1-hr incubation with Metopirone, hydroxylation of progesterone into DOC increased and the synthesis of B decreased. Preincubation and a 2-hr incubation with Metopirone caused a decrease in the synthesis of B, 18-OH-B and 18-OH-DOC and an increase in DOC. The results constitute direct evidence of the ability of the fetal adrenal glands to synthesize all corticoids and indicate that most probably corticoids are synthesized by the fetal adrenal glands in the same way as in the adrenals of adult animals.

Significance of the Biphasic Developmental Pattern of the Hypothalamo-Pituitary-Adrenocortical System in the Rat

One group of neonatal rats was injected with metopirone at 2-5 days and the second group at 7-10 days of age. At 14 and 21 days all rats treated with metopirone had reduced body and adrenal weights in comparison with their saline-treated littermates. At 21 days the smallest adrenals were in the rats treated with metopirone at 7-10 days. Metopirone increased resting and stress levels of adrenal and plasma corticosterone in the 14-day-old rats and the response to stress by the adrenal corticosterone increase in the 21-day-old rats. The differential effect of metopirone applied in two developmental periods was indicated.

Pituitary and Adrenal Glands in Neonatal Rats Studied by Metopirone (Su4885)

One half of each litter of the 2- and 7-day-old rats was injected twice daily for 3 consecutive days with 15 mg/100 g body weight of metopirone (MET) in 0.05 ml of saline, and the remaining littermates with saline only. At the ages of 5 and 10 days, one half of the pups was sacrificed immediately, and the second half 20 min after s.c. injection of histamine as a stressor. MET depressed body weight and induced adrenal hypertrophy in the 5- and 10- day-old rats, and pituitary hypertrophy in the 5-day-old rats only. In resting condition the adrenal glands of the 5-day-old rats treated with MET contained less corticosterone (determined fluorometrically) than the 5-day-old control and the 10-day-old pups treated also with MET. Furthermore, neonatal MET treatment induced (histamine) stress response by the increase in adrenal corticosterone content in the 10-day-old rats, and by the increase in corticosterone content in plasma in both ages. The results indicate high sensitivity of the young neonatal rats to hormonal manipulations. They also yield additional support to the concept of functional integrity of the hypothalamo-pituitary-adrenocortical system in neonatal rats, and to the flexibility of the postnatal developmental pattern of stress response.