J. Hotchkiss

Periparturitional serum concentrations of prolactin, the gonadotropins, and the gonadal hormones in the rhesus monkey.

Summary The time courses of serum concentrations of prolactin, estradiol, estrone, progesterone, LH, and FSH were studied in seven pregnant rhesus monkeys from 1 month prior to delivery until 1 month after parturition. All animals nursed their young. Circulating levels of estradiol and estrone increased during the last few days of pregnancy, reaching peak values of 700 pg/ml and 350 pg/ml, respectively, on the day prior to delivery, fell precipitously to about 25 pg/ml within 1 day after parturition, and remained at this level for at least 30 days. Serum prolactin concentrations also increased during the week preceding parturition, rose abruptly at delivery, and then declined gradually. Serum progesterone levels ranged between 2 and 3 ng/ml during the last month of pregnancy, rose slightly a few days prior to parturition, decreased sharply at delivery to 50% of pre-partum levels and declined gradually thereafter. Serum LH and FSH levels were not detectable during the entire sampling period. The administration of estradiol benzoate to two pregnant monkeys at midgestation, in a manner which replicated the normal prepartum increase in serum estradiol concentrations, failed to elicit an elevation in circulating prolactin levels or to induce premature delivery of the fetus. We are indebted to E. Burkett, B. Leeson, C. Tsai, L. Morrison, and to our animal care staff for their expert technical assistance.

On the mechanism of lactational anovulation in the rhesus monkey

The relative roles of infant suckling and of maternal prolactin (PRL) secretion in lactational anovulation were studied in ovary-intact and ovariectomized rhesus monkeys nursing young that had been removed from their natural mothers. Hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator activity was monitored electrophysiologically in freely behaving animals by radiotelemetry. Serum luteinizing hormone, PRL, estradiol, and progesterone were also measured. Suckling inhibited GnRH pulse generator activity and ovarian cyclicity in all ovary-intact females but had no such effect on the pulse generator in long-term ovariectomized animals. When PRL secretion was suppressed by daily bromocriptine administration, GnRH pulse generator activity remained significantly inhibited and ovulation was prevented in four monkeys (6 trials), whereas in two females (6 trials) a rapid increase in pulse generator frequency and the resumption of ovarian cyclicity were observed although suckling activity was maintained. One monkey displayed both response types. Although these results indicate that suckling per se is able to restrain GnRH pulse generator activity in the absence of PRL, they also suggest that the relative importance of these determinants is variable depending on factors that remain to be determined. The present study also confirms the permissive role of the ovary in the lactational suppression of GnRH pulse generator activity.The relative roles of infant suckling and of maternal prolactin (PRL) secretion in lactational anovulation were studied in ovary-intact and ovariectomized rhesus monkeys nursing young that had been removed from their natural mothers. Hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator activity was monitored electrophysiologically in freely behaving animals by radiotelemetry. Serum luteinizing hormone, PRL, estradiol, and progesterone were also measured. Suckling inhibited GnRH pulse generator activity and ovarian cyclicity in all ovary-intact females but had no such effect on the pulse generator in long-term ovariectomized animals. When PRL secretion was suppressed by daily bromocriptine administration, GnRH pulse generator activity remained significantly inhibited and ovulation was prevented in four monkeys (6 trials), whereas in two females (6 trials) a rapid increase in pulse generator frequency and the resumption of ovarian cyclicity were observed although suckling activity was maintained. One monkey displayed both response types. Although these results indicate that suckling per se is able to restrain GnRH pulse generator activity in the absence of PRL, they also suggest that the relative importance of these determinants is variable depending on factors that remain to be determined. The present study also confirms the permissive role of the ovary in the lactational suppression of GnRH pulse generator activity.

Effects of Naloxone on Estrogen-Induced Changes in Hypothalamic Gonadotropin-Releasing Hormone Pulse Generator Activity in the Rhesus Monkey

In the ovariectomized rhesus monkey, estradiol (E2) markedly reduces the frequency of the GnRH pulse generator as monitored by LH pulse frequency and the concurrent changes in hypothalamic electrical activity, an action mimicked by morphine. In addition, the duration of the increments in multiunit electrical activity (MUA volleys) that precede each LH pulse is decreased by estrogen administration, an action also shared by morphine. The role of endogenous opioids in these actions of E2 was investigated in 8 ovariectomized animals restrained in primate chairs. They were fitted with indwelling cardiac catheters and with bilateral arrays of recording electrodes chronically implanted in the mediobasal hypothalamus. Physiological serum E2 levels achieved by subcutaneous implantation of E2-containing Silastic capsules increased MUA volley interval from 50.8 +/- (SEM) 1.6 min in the control period to 81.1 +/- 6.2 min following E2. Mean MUA volley duration decreased from 21.9 +/- 1.0 to 13.0 +/- 0.7 min. The placement of empty Silastic capsules had no effect on MUA volley duration or interval. Naloxone administration (2.5 mg bolus followed by a 1 mg/h infusion lasting 4-8 h) completely (n = 4) or partially (n = 2) blocked the effects of E2 on MUA volley interval in 6 of the 8 monkeys, and was without effect in the remainder. In contrast, however, naloxone had little or no effect on the action of E2 on MUA volley duration, (13.0 +/- 0.7 vs. 14.0 +/- 0.9 min). These findings suggest that the inhibitory action of E2 on GnRH pulse generator frequency, like that of all other gonadal steroids studied to date, may be mediated by endogenous opioids.(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolic clearance rate of progesterone during lactation in the Rhesus monkey.

Summary No difference in the MCR of progesterone was observed in the follicular and luteal phases of the menstrual cycle in the rhesus monkey. In lactating animals, however, the MCR was increased by 30%. This increase is insufficient to account for the 20-fold difference in circulating progesterone levels in luteal phase and lactating animals.

Hypothalamic Control of the Menstrual Cycle

The relation between ovarian function and menstruation did not become clear nor widely accepted until the early twentieth century, and the details of this relation as currently understood are amply covered in other chapters in this volume. The next conceptual step forward in reproductive physiology came when it became evident that the ovary did not function autonomously, but depended upon the presence of the anterior pituitary gland. The concept of anterior pituitary ommipotence could not survive, however, in the face of the clever experimental designs of Harris (1955) who showed that ovulation in the rabbit could be induced by sensory signals arising in the periphery which were translated by the hypothalamus into hormonal signals from the pituitary gland. The isolation, characterization, and synthesis of the hypothalamic gonadotropin-releasing hormone (GnRH) and a myriad of other hypothalamic hormones that regulate the secretion of other anterior pituitary hormones have added substance to the original theories of the hypothalamic control of pituitary function.