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SUMMARY During the day of pro-oestrus in rats showing regular 4-day oestrous cycles, the concentration of progesterone in peripheral plasma increased slowly from 09.30 to 13.30 h and more rapidly during and after the 'critical period' for luteinizing hormone (LH) release to reach a level of 24·4 ng/ml at 21.00 h. Administration of sodium pentobarbitone at 07.00 or 13.30 h (but not at 16.30) on the day of pro-oestrus delayed ovulation and also prevented the rise in progesterone concentration at 21.00 h on that day. Levels were found to be high 24 h later on the evening of the day preceding the delayed ovulation. It is concluded that the major rise during and after the 'critical period' is the result of LH stimulation of ovarian progesterone secretion. The possibility that the gradual increase in peripheral plasma progesterone concentration that occurred before the 'critical period' was due to adrenal secretion and played some role in facilitating the onset of the ovulatory surge of LH was examined. The rise in plasma corticosterone concentration roughly paralleled that of progesterone up to the 'critical period' but the curves for the two steroids later became divergent. Suppression of adrenal activity during pro-oestrus by the administration of dexamethasone phosphate resulted in a blockade of ovulation which could be reversed by the administration of either progesterone or corticotrophin (ACTH). Conversely, blockade of ovulation followed ACTH administration at metoestrus and approximately 50% of animals adrenalectomized or sham-adrenalectomized at metoestrus or dioestrus failed to ovulate at the expected time. In adrenalectomized rats tested 12–15 days after operation, the period of pro-oestrus during which sodium pentobarbitone administration could block ovulation was more prolonged than in intact rats. The possible roles of progesterone of adrenal origin in facilitating LH release and entraining the LH release mechanism to the light—dark rhythm and of progesterone of ovarian origin in ensuring full sexual receptivity are discussed.

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SUMMARY Plasma and pituitary luteinizing hormone (LH) concentrations were measured by radioimmunoassay at different stages of the normal 4- and 5-day oestrous cycle of rats. Plasma levels were low except between the afternoon of pro-oestrus and the morning of oestrus when levels were high but variable. Pituitary LH content and concentration were less consistent but averaged values showed a steady rise from a low level after ovulation to a peak on the afternoon of pro-oestrus, and a rapid fall that evening when plasma levels rose rapidly. No significant differences were observed in plasma LH between 4- and 5-day cycles; in particular there was no reduction at metoestrus or dioestrus-1 or increase on the evening of dioestrus-2. Plasma oestradiol was already high on the morning of dioestrus-2 in some rats and in all rats by that evening. On the morning of pro-oestrus in the 5-day cycle, plasma oestradiol was still high but somewhat lower than at the corresponding stage in the 4-day cycle. Blocking ovulation by administration of sodium pentobarbitone at prooestrus in a 4-day cycle prevented the rise in plasma LH and the fall in pituitary content. Blocking generally failed in animals whose plasma LH had reached the level of 20 ng/ml or more at the time of injection. Plasma oestradiol levels on the morning of the expected day of oestrus were higher than normal in animals in which ovulation was blocked by pentobarbitone but were below pro-oestrous values. In the anovulatory state induced by exposure to constant light no major increase in plasma LH was detected after 24 days of illumination or after 3 months exposure. Animals rendered anovulatory by injection of testosterone propionate on the 4th day of postnatal life had low plasma LH levels as adults. All three groups had a low pituitary LH content. The animals exposed to long-term light and those treated with androgen generally had plasma oestradiol concentrations below the peak levels seen on the morning of pro-oestrus in the normal cycle.

Adult female albino rats were exposed to constant illumination of moderate intensity for 55\p=n-\65 days; at the end of this period more than 95 % had no macroscopically visible luteal tissue in their ovaries and more than 90 % were sexually receptive. In these animals ovulation was consistently induced by mating. The major component of the mating pattern responsible for the induction of ovulation was penile intromission. Mounting without intromission was much less effective and the occurrence or non-occurrence of ejaculation did not affect the incidence of ovulation. Non-sexual 'stressful' stimuli or the injection of progesterone also induced ovulation in about 50% of animals. However, adrenal progesterone was not required for either the maintenance of sexual receptivity or mating-induced ovulation since adrenalectomized rats exposed to constant light also mated and ovulated.The time-course of the secretion of luteinizing hormone (LH), determined by radioimmunoassay of plasma LH, also indicated that mating had effects on LH secretion independent of any action of progesterone. LH concentrations were high at 40 min and maximal at 60 min after mating but decreased thereafter while following the injection of progesterone the levels rose gradually and remained high until at least 360 min after the injection. Sodium pentobarbitone administration had little effect on LH secretion induced by mating but blocked ovulation in some animals. Mating-induced ovulation was not invariably associated with increased activity of the thyroid gland but an increase did occur when the mating stimulus was prolonged.

Male rats given 250 mug oestradiol benzoate by subcutaneous injection on Day 4 of postnatal life showed a marked delay in the onset of the pubertal increase in the weight of the testes and seminal vesicles and in spermatogenesis but not a complete failure of sexual development. The increase in plasma testosterone concentration at puberty was also delayed in oestrogen-treated males but the eventual increase in seminal vesicle weight was closely related in time to the delayed increase in plasma testosterone concentration. Both plasma LH and FSH concentrations were reduced for about 10 days after oestrogen administration as compared to control values. After 22 days of age, plasma LH concentration did not differ significantly from the control values. The plasma FSH concentration of the oestrogen-treated males showed a delayed rise to values equal to or higher than those of controls of the same age. The delayed rise in plasma FSH concentration in the oestrogen treated males preceded the delayed rise in plasma testosterone in these animals. The decrease in plasma FSH concentration from the high prepubertal values to the lower values in adults occurred at different ages in the control and in oestrogen-treated rats but in both groups the decrease occurred as plasma testosterone levels were increasing and the first wave of spermatogenesis was reaching completion. The increase in plasma FSH concentration after castration was reduced in oestrogen-treated males during the period throughout which FSH levels in the intact animals were subnormal but the levels in oestrogen-treated males castrated after the delayed rise in FSH had occurred did not differ from control values. It is suggested that the delayed sexual maturation of male rats treated with high doses of oestrogen in the neonatal period is related principally to abnormalities in the secretion of FSH.

Many workers have shown that thyroid activity is altered by physical damage. However, there is no direct evidence that such stress affects the rate of release of thyroid hormone from the gland. As part of a study on the functional relationship between the central nervous system, anterior pituitary gland and thyroid gland a method has been devised for studying the rate of output of thyroid hormone in conscious rabbits (Brown-Grant, von Euler, Harris & Reichlin, 1954). In the experiments to be described the effects of both emotional and physical stress on the rate of release of thyroid hormone in the rabbit have been studied. METHODSThe technique used for studying thyroid activity in unanaesthetized rabbits has been described previously (Brown-Grant, von Euler, Harris & Reichlin, 1954). As in the previous work the animals were maintained on a standard diet and at a constant environmental temperature. Emotional stress has been produced by: (1) applying brief subcutaneous electric shocks (faradism) at approximately 1 min intervals. During the period of stimulation the animals were partially immobilized by placing them in small wire cages. The intensity of the stimulus was just sufficient to cause signs of fright. (2) Restraining the animals, either by confining them in a small cage, or by tying the back legs to the side of the cage with wide gauze bandages. In most experiments the two types of restraint were used alternately for periods from 24 to 72 hr, since the effect of any one procedure tended to wear off. (3) Subjecting the animals to abrupt changes in lighting, either from the normal day/night alternation to continuous darkness, or from continuous illumination to continuous darkness, or from continuous darkness to continuous illumination. All stresses were continued for at least 24 hr as it was noted that measurable changes in thyroid activity do not occur within shorter periods.Physical stress has been produced by: (1) removing 20 % of the estimated blood volume from the marginal vein of the ear on either a single occasion or on two consecutive days. (2) Subjecting the animal to laparotomy under ether anaesthesia, and (3) giving an intraperitoneal injection of 1-0 ml. turpentine (which produced no visible signs of pain or discomfort).