The dynamics of ovarian and pituitary hormone changes during the midcycle period were evaluated. Changes in hormone levels were determined at 2-h intervals for 5 consecutive days during the periovulatory phase of the cycle in five women. During the 50 h preceding the onset of the surge, the rates of increments for estradiol (E2), progesterone (P4), and LH were similar, with doubling times of 57-61 h. The onset of LH and FSH surges was found to occur abruptly (LH doubled within 2 h). They were temporally associated with the attainment of peak E2 levels and occurred 12 h after the initiation of a rapid rise of P4. The mean duration of the surge was 48 h, with a rapidly ascending limb (doubling time, 5.2 h) lasting 14 h accompanied by a rapid decline of E2 and a continued rise of P4. The surge was followed by a peak plateau of gonadotropin levels lasting for 14 h and a transient leveling of P4. The longer descending limb (half-time, 9.6 h), lasting for 20 h, was associated with a second rapid rise of P4, beginning 36 h after surge onset or 12 h before termination of the surge. By using the onset of the LH surge as a reference point, our data provide a relatively precise picture of the hormonal changes preceding the onset of the gonadotropin surge and the temporal relationship between the multiphasic P4 rise and pituitary-ovarian function.

Information on the relative activity and on the functional relationships between the acutely releasable (1st) and reserve (2nd) pools of pituitary LH during the course of the normal menstrual cycle was obtained via a 4 h LRF infusion (0.2 mug/min X 4 h). This was immediately followed by 3 pulses of LRF (10 mug at 2 h intervals) to assess further the size of the acutely releasable pool after activation of the reserve pool by the infusion. Our observations indicate that two functional pools of LH are present in all phases of the menstrual cycle and that comparative pool size or activity is influenced profoundly by ovarian steroid feedback as well as by the pattern of input of hypothalamic LRF. From the early to the late follicular phase, in synchrony with the rising levels of E2, the size of the 2nd pool is preferentially augmented. A small increase in the 1st pool activity is not apparent until the late follicular phase when a 5-fold increase in the size of the 2nd pool is also attained. During the mid-luteal phase and in association with relatively high progesterone (P) and E2, th large 2nd pool is maintained as in the late follicular phase but the 1st pool is strikingly smaller. Activation of the 2nd pool of LH by the LRF infusion (priming) increases the acutely releasable LH (1st pool) in all three phases of the cycle, as evidenced by an enhanced response to the 1st but not subsequent pulses of LRF at the end of the infusion as compared with non-infused controls. This priming effect is likely a reflection of activation or "shifting" of LH from the larger 2nd pool to the smaller 1st pool. It is found that this priming effect is greatest during the mid-luteal phase as compared to other phases of the cycle. During the days of mid-cycle LH surge, a dramatic reversal of the relative activity of the two pools in observed and this is manifested by an enormous increase in the activity of the 1st relative to the 2nd pool. In contrast to other phases of the cycle, the release of LH from the 2nd pool is not sustained and this premature decline in LH release despite continuous LRF infusion appears to be due to pituitary depletion of LH as evidenced by the failure of the pituitary response to pulses of LRF immediately following the infusion...

The disappearance rate of the immunoreactive beta h-endorphin and the effects of beta h-endorphin on pituitary hormone secretion were investigated in normal volunteers. Synthetic human beta h-endorphin was administered as a 2.5-mg iv bolus to five normal women resulting in a 1000-fold increase in concentration of circulating immunoreactive beta h-endorphin within 2.5 min. This was followed by a triple exponential disappearance curve yielding an initial fast component with a half-time (t 1/2; +/-SD) of 4.1 (+/-0.6) min, a midrange component with a t 1/2 of 13.1 (+/-0.6 min, and a slow component with t 1/2 of 46.2 (+/-7.0) min. In both male and female subjects this dose of beta-endorphin induced a significant increase in the levels of PRL and a significant decline in the concentration of LH, without altering basal levels of GH and TSH.

To examine the relationship between the priming and releasing actions of LRF on LH secretion, 14 normal cycling women received 4 different rates of LRF infusion (0.005, 0.01, 0.05, and 0.1 microgram/m2.min for 4 h). The releasing action of the infusion was measured as the area under the curve and the priming effect was assessed by the acute LH increment in response to a test pulse of LRF (10 microgram) at the end of infusion. At the lower 2 infusion rates, there were only minor changes in releasing function, but it increased exponentially (r = 0.986) with higher rates of infusion. In contrast, the priming effect of the lower 2 doses of infusion increased markedly as a function of infusion rate, but no additional priming was found with the higher rates of infusion. Thus, over the range of infusion rates employed, the releasing and priming functions of LRF appear to be dose dependent. These results indicate that the interdependent releasing and priming actions of LRF on LH secretion are functionally dissociable and that large elevations of LRF tend to favor release, while small LRF increments seem to promote priming preferentially.

The 24-h patterns of plasma concentration change in dopamine (DA) and its immediate deaminated metabolite, dihydroxyphenylacetic acid (DOPAC), were determined in 6 normal women (16 studies) by a modified radioenzymatic assay. Changes in DOPAC levels exhibited a marked circadian rhythm, with peak during the day and a nadir at night. At 1200 h, the DOPAC concentration increased significantly (P less than 10(-4)) to a peak value 62.9 +/- 8.4 ng/ml) 117% higher than the 24-h mean. At 2200 h, plasma DOPAC decreased (P less than 10(-4)) to a nadir concentration (10.0 +/- 3.3 ng/ml) 66% lower than the 24-h mean. The circadian rhythm of DOPAC could be reproducibly demonstrated over at least 4 successive days in individual subjects. There were no well defined circadian variations in plasma concentrations of DA. Since the plasma DOPAC concentration appears to reflect central nervous system dopaminergic neuronal activity, the present demonstration of a circadian rhythm of plasma DOPAC suggests that the activity of central nervous system DA-containing cells is higher during the day than at night.