Lower rates of academic productivity, more time spent in teaching and patient care and less time spent in research, less institutional support for research, and lower rates of specialization in highly paid subspecialties contributed to the lower ranks and salaries of female faculty members.

We measured plasma insulin-like growth factor I/somatomedin-C (IGF-I/SmC) concentrations and mean 24-h GH secretion serially before and during therapy with the long-acting somatostatin analog SMS 201-995 in 21 patients with acromegaly. When mean plasma GH was elevated above 12.0 +/- 0.6 (+/- SE) micrograms/L, plasma IGF-I/SmC concentrations were uniformly high, but a decline of mean plasma GH below this value was accompanied by a linear decrease in IGF-I/SmC concentrations (r = 0.89; P less than 0.001). Even mildly abnormal mean GH concentrations (greater than 4.6 but less than 10 micrograms/L) were accompanied by high plasma IGF-I/SmC values. The log dose-response interrelation between mean 24-h plasma GH and IGF-I/SmC concentrations was linear (r = 0.86; P less than 0.001). We conclude that 1) an excellent log dose-response correlation between mean 24-h plasma GH and IGF-I/SmC concentrations is present in patients with acromegaly; 2) normalization of plasma IGF-I/SmC occurs only in patients with mean daily GH output within the normal range; and 3) determination of plasma IGF-I/SmC is an accurate indicator of normalcy of GH secretion and should be used in the diagnosis of active acromegaly as well as in monitoring the progress of therapy.

Hypothalamic amenorrhea (HA) is a clinical disorder of unknown etiology. The diagnosis is made by exclusion of known abnormalities of pituitary and ovarian function. To determine if abnormalities of GnRH secretion could account for the anovulation and amenorrhea, we measured plasma gonadotropins every 20 min for 10- to 24-h periods in 19 women with HA. Ovarian steroids and gonadotropin responses to an iv bolus dose of GnRH (25 ng/kg) were also measured. The results were compared to those obtained during the early follicular (EF) and late luteal (LL) phases of ovulatory cycles in normal women. Plasma estradiol was lower (mean +/- SE, 52 +/- 5 pg/ml) than either cycle stage in normal women. Mean plasma LH was lower than EF values and FSH was higher than LL values. The amplitude of LH pulses in HA was similar to that in normal women. LH pulse frequency was the same as that present during the LL, but lower than that during the EF (HA, 4.7 pulses/12 h; EF, 7.7 pulses/12 h; P less than 0.05). In addition to the similar frequency, the patterns of LH secretion in HA resembled that of LL in that the amplitude of LH pulses was highly variable and pulses occurred at irregular intervals. Consistent changes in diurnal gonadotropin secretion were not found, and LH secretion was greater at night in 9 studies and during the day in 5 studies. Repeat studies in three patients (5-13 months later) revealed that LH pulse frequency was variable, being unchanged in 1, increased in 1, and decreased in the third patient. Thus, LH pulse frequency and, by inference, GnRH pulse frequency are similar in HA to those in the normal luteal phase despite a different steroid milieu. GnRH pulse frequency increases from the luteal to the follicular phases of normal cycles and may be important in the initiation of ovarian follicular maturation. These data suggest that the absence of cyclical gonadotropin secretion and anovulation in HA result from a decreased frequency and irregular amplitude of GnRH secretion and consequent absence of ovarian follicular maturation.

Pulsatile secretion of LH and FSH was examined to determine if the frequency of LH pulses, and by inference pulsatile GnRH secretion, varied during the human menstrual cycle. Blood samples were obtained at 10- or 20-min intervals for 12 or 24 h at 7-day intervals during the same ovulatory cycle in eight normal women. Ovarian steroids showed the expected cyclical changes and mean plasma FSH concentrations showed an inverse relationship to estradiol, being low when estradiol was greater than 150 pg/ml. Sampling every 10 min revealed a constant LH pulse amplitude but LH pulse frequency increased (from 11.8 to 14.3 pulses/12 h) during the follicular phase. LH pulse frequency was not further increased in two women sampled during the LH surge, but pulse amplitude was markedly higher. During the luteal phase LH pulse frequency was reduced to eight pulses/12 h but frequency was more variable between subjects than in the follicular phase. LH pulse amplitude showed striking variation (0.8-29.4 mIU/ml) during the luteal phase of the cycle and large LH secretory episodes which lasted 1-3 h were irregularly interspersed among periods of low amplitude LH secretion. These data show that the frequency of LH pulses, and by inference GnRH secretion, varies during the menstrual cycle but the degree of change is less than reported in previous studies. This observation may explain the reported efficacy of fixed frequency GnRH regimes in inducing ovulation and cyclical ovarian function.

To elucidate further pituitary influence on testicular function, we studied the effect of PRL, GH, and LH alone or in various combinations on the maintenance of testicular LH receptor concentration and testosterone synthesis in response to LH (testicular responsiveness) in hypophysectomized adult rats. Hypophysectomy reduced LH receptor concentration by 80% and testicular responsiveness to LH by 70% 7 days after surgery. Treatment with PRL (75 or 150 iig/day) or with GH (75 or 150 iig/day) initiated within 6 h after surgery and continued twice daily for 6 days partially prevented the loss of LH receptors. The effect of PRL (150 jug/day) plus GH (150 /xg/day) on LH receptor concentration was additive. The combination of LH (5 jug/day), PRL, and GH prevented any loss of LH receptors after hypophysectomy. A positive effect of LH on its receptor occurred in the presence of PRL. Treatment of hypophysectomized rats with 5 /ng LH plus 150 /ng PRL enhanced the effect observed with PRL alone (1.31 pmol/testis vs. 1.68 pmol/testis, P < 0.05). We previously reported that administration of 5, 25, or 50 /xg LH/day to hypophysectomized rats caused a further