Two adult men with feminizing adrenal cortical carcinoma had measurements of their 24-h plasma corticosteroid and gonadotropin patterns as well as 24-h mean hormone levels of estradiol, estetrol, 11-desoxycortisol, DHEA-S, DHEA and testosterone. Cortisol, 11-desoxycortisol and estrogen production rates were also measured. The 24-h corticosteroid patterns showed preservation of the normal 24-h episodic and circadian patterns, albeit at higher levels. The cortisol production rates were markedly elevated despite only moderate elevation of the 24-h mean cortisol level. There were elevated plasma 11-desoxycortisol levels and a markedly elevated 11-desoxycortisol production rate in one patient and THS excretion in the other. The plasma estradiol levels, urinary excretion and production rates were markedly elevated. In addition, there was a decrease in the specific activity of estriol compared with estrone and estradiol as well as measurable levels of estetrol in both patients. These latter observations coupled with the urinary immunoassayable hCG in one patient suggest that these tumors may be functioning like trophoblastic tissue. The possibility that estetrol may serve as an additional marker for tumors of trophoblastic origin is of additional interest.
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 usefulness of timed 3-hour urine collections as a substitute for serum gonadotropin (LH and FSH) determinations during the menstrual cycle and during LHRH testing was examined. The timing of the 3-hour urine collection is not important in mature individuals, since no significant temporal trend was found when aliquots were collected every 3 hours throughout two 24-hour periods in one mature woman. Good correlation was found between serum LH and FSH concentrations and the quantity of LH and FSH in timed 3-hour urine specimens throughout normal, ovulatory menstrual cycles in two women. Studies before and during 51 LHRH stimulation tests in normal men, children, and women during different phases of the menstrual cycle and in patients with a variety of hypothalamic-pituitary-gonadal axis disorders were performed. There was good correlation between the quantity of the gonadotropins in time 3-hour urine collections and the mean serum LH and FSH concentrations before and during the LHRH test. The "response area" for serum LH and FSH also correlated well with the amounts of LH and FSH in the urine collected during this period. Therefore, the timed 3-hour urine collection for gonadotropin estimation provides a simple, accurate method for the integration of fluctuating serum concentrations of LH and FSH during such instances of physiologic variability as the menstrual cycle and LHRH stimulation tests.
The possible role of fluctuations in serum estrogen concentrations in the regulation of prolactin secretion was investigated by comparing phenothiazine-stimulated prolactin secretion in normal women during the early follicular phase and the late follicular phase of the menstrual cycle. There was little difference between early follicular phase concentrations of prolactin (17 +or- 4 ng/ml) and late follicular phase concentrations (20 +or- 2 ng/ml). Following the administration of phenothizine, prolactin levels were significantly (P greater than .02) higher at mid-cycle (402 +or- 46 ng/ml/hour) than in the early follicular phase (317 +or- 46 ng/ml/hour). The results suggest that endogenous estrogen secretion may be involved in the regulation of serum concentrations of prolactin in humans.
Progesterone binding by 100,000 X g cytosols of human myometria from patients undergoing hysterectomy for various reasons was assayed using equilibrium dialysis or DEAE-cellulose filtration. The estimates of high-affinity porgesterone binding obtained by both techniques showed a significant correlation. Dialysis and filtration assays with cortisol competing with [3H]progesterone for binding indicated that the specific progesterone binding by the cytosols was the result of progesterone interaction with two high-affinity constitutents. Myometrial cytosols from tissues under progestin stimulation (secretory endometrium or pregnancy) had low concentrations of progestin binders. Cytosols from uteri with atrophic endometrium showed consistently high concentrations of progestin binders and those tissues under estrogen stimulation (proliferative endometrium or hyperplasia) and variable binder concentrations. No differences were detected between grouped observtions classified into 10 clinical categories. The DEAE-cellulose filtration is an effective method for evaluating progesterone binding which uses well-established statistical techniques and requires less tissue, less time for incubations, and fewer points for reliable analysis than does equilibrium dialysis.
