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To test the effect of opiate receptor blockade on hormone release in man, we administered 10 mg naloxone iv to eight normal subjects and compared the results with those found after saline infusion. Naloxone produced a rise in serum cortisol (P < 0.01), LH (P < 0.01), FSH (P < 0.05), and insulin (P < 0.05) levels but did not alter serum GH, PRL, TSH, arginine vasopressin, glucagon, T3, or T4. Naloxon e had no effect on GH levels in two subjects with active acromegaly or on TSH levels i n six subjects with primary hypothyroidism. In dynamic pituitary function testing, naloxone diminished the GH response to arginine (P < 0.05) without altering the PRL response; naloxone augmented the PRL response to TRH (P < 0.025) without affecting the TSH response. Naloxone did not significantly alter GH or PRL response to L-dopa. Naloxone enhanced the increment in serum cortisol induced by the stress of gastroscopy without changing the GH or PRL response. Naloxone increased glucose response areas (P < 0.05) after an iv gl...

Concentrations of pregnenolone (delta5P), dehydroepiandrosterone (DHEA), 16alpha-hydroxydehydroepiandrosterone (16alpha-OH DHEA), pregnenolone sulfate (delta5P-S), and dehydroepiandrosterone sulfate (DHEA-S) were measured simultaneously by radioimmunoassay in individual, paired umbilical artery (UA) and vein (UV) sera from 18 normal term pregnancies, 6 in labor, 12 not in labor. Mean UA and UV levels +/- SEM (ng/ml) were for delta5P: 30.39 +/- 1.69, 35.55 +/- 3.06; DHEA: 12.31 +/- 2.34, 3.66 +/- 0.38; 16alpha-OH DHEA: 7.48 +/- 0.63, 10.59 +/- 0.78; delta5P-S: 1,652 +/- 154, 1,486 +/- 130; DHEA-S: 2,122 +/- 134, +/- 134, 1,906 +/- 134. Umbilical artery delta5P-S, DHEA-S, and DHEA levels were significantly higher than UV levels, whereas the reverse was true for delta5P and 16alpha-OH DHEA. The inverse arterio-venous (A-V) gradient for 16alpha-OH DHEA was contrary to previous published reports using pooled samples. Comparison by linear regression of paired UA and UV steroid concentrations of delta5P, delta5P-S, DHEA, and DHEA-S revealed a significant correlation (P less than 0.01) for each steroid. Labor was associated with a significant increase in UA levels of DHEA-S and a smaller, but not quite significant, increase in UA levels of delta5P-S, while similar changes for unconjugated delta5-3beta-hydroxysteroids were not observed. Mean A-V gradients between the group of patients in labor and those not in labor were not significantly different. These data demonstrate that: 1) a significant difference between UA and UV concentrations exists for delta5P, DHEA, 16alpha-OH DHEA, delta5P-S, and DHEA-S; 2) there is a significant correlation between UA and UV concentrations for delta5P, DHEA, delta5P-S, and DHEA-S, implying that each fetoplacental unit maintains an equilibrium relative to these steroid concentrations in the umbilical circulation; 3) labor is associated with a significant increase in UA levels of DHEA-S and probably of delta5P-S.

Twelve hyperprolactinemic women were administered the α aminoergoline derivative, CU 32-085 (Sandoz, Inc., East Hanover, NJ), in order to determine its effect on prolactin (PRL) secretion. The mean pretreatment serum PRL level was 145.0 ± 11.5 ng/ml. Significant declines of serum PRL occurred with total daily doses of CU 32-085 of 0.1 to 0.5 mg ( P

Over a period of two and a half years, 34 women with galactorrhea or amenorrhea, all with an abnormal sellar polytomogram, underwent transsphenoidal microsurgical exploration of the sella. Eighteen women and microadenomas (less than or equal to 1 cm. in diameter), seven had macroadenomas (greater than than 1 cm. in diameter), and five had unidentified lesions. Only one women had a normal pituitary gland. Three women had cryosurgery without biopsy. Preoperatively, hyperprolactinemia occurred in 24 of 25 women with adenomas and two of five with nonadenomatous lesions. There were no operative deaths. Significant morbidity occurred in only three patients, none of whom had microadenomas. Postoperatively, menses resumed in 16 of the 17 women with microadenomas and in two of the seven with macroadenomas who presented with amenorrhea. Galactorrhea disappeared in 15 of the 17 women with microadenomas and in four of the seven with macroadenomas who presented with galactorrhea. In five patients with unidentified lesions, a return of menses occurred in two of four with previous amenorrhea, and galactorrhea abated in two of three who presented with lactation. We conclude that sellar polytomography in women with hyperprolactinemia is a useful technique technique for the diagnosis of pituitary adenomas, a lesion which may occur more frequently than previously realized. In addition, transsphenoidal microresection of microadenomas is safe and effective.The detection, evaluation, and treatment of pituitary microadenomas in women with galactorrhea and amenorrhea are discussed. All of the women had an abnormal sellar polytomogram and underwent transsphenoidal microsurgical exploration of the sella. 18 women had microadenomas of 1 cm or less in diameter, 7 had macroadenomas greater than 1 cm in diameter, and 5 had unidentified lesions. Only 1 woman had a normal pituitary gland. 3 women had cyrosurgery without biopsy. Preoperatively, hyperprolactinemia occurred in 24 of 25 women with adenomas and 2 of 5 with nonadenomatous lesions. Comparison of serum prolactin values and tumor size by linear-regression analysis revealed a positive correlation (p .05, r=.69). Marked morbidity occurred in 2 patients with macroadenomas and in 1 patient treated by cyrosurgery. Postoperatively, menses resumed in 16 of the 17 women with microadenomas and in 2 of the 7 with macroadenomas who presented with amenorrhea. Galactorrhea disappeared in 15 of the 17 women and in 4 of 7 who presented with galactorrhea. In 5 women with unidentified lesions a return of menses occurred in 2 of 4 with previous amenorrhea, and galactorrhea abated in 2 of 3 who presented with lactation. It is concluded that sellar polytomography in women with hyperprolactinemia is a useful technique for the diagnosis of pituitary adenomas and that transsphenoidal microsection of microadenomas is safe and effective.

Three patients with hyperprolactinemia and large extrasellar pituitary macroadenomas were treated with bromocriptine, 10 mg daily, for 8 weeks. In spite of correction of their amenorrhea, galactorrhea, and hyperprolactinemia, radiologic evaluation by CT scan failed to show evidence of tumor shrinkage. After surgical resection, histologic examination revealed that PRL-secreting cells comprised only a small portion of the tumor cell population in two patients and in the third patient were completely absent. These cases illustrate that large nonfunctional pituitary tumors may mimic signs and symptoms of a prolactinoma and stress the importance of adequate radiologic evaluation during medical management. 8 references, 3 figures.

This report describes aggregate time trend effects of advancing gestational age on circulating maternal concentrations of 17beta-estradiol (E2), estriol (E3), dehydroepiandrosterone (D), dehydroepiandrosterone sulfate (D-S), delta 5-androstenediol (delta 5 diol), delta 4-androstenedione (delta 4 A), testosterone (T), and dihydrotestosterone (DHT) in a sequential series of 155 blood samples obtained from 19 normal pregnant women ranging from 26-40 weeks gestational age. Only E2, E3, and D-S show aggregate time trend effects. Log (E2) plots as a linear positive sloping curve from 26-40 weeks. Log (E3) plots as a positive sloping curve that is significantly steeper than log (E2) (P less than 0.05). Log (D-S) plots into a negative sloping curve which mirrors the pattern for log (E2) but cannot be statistically associated with log (E2) except for the opposite sign of their slopes, which are both significantly different from a zero slope (P less than 0.05). delta 4 A, T, DHT, delta 5 diol, and D show no aggregate time trends; however wide, comoving undulations for delta 4 A, T, DHT, and delta 5 diol between 26-28 and 38-40 weeks are confirmed in time by comparison of log mean plots and in magnitude by regressing the C19 steroids on one another. D shows virtually no association with the other C19 steroids. All C19 steroids, except for T, circulate at nonpregnant concentrations, implying that there is little placental secretion of these steroids into the maternal circulation.

Hypocycloidal tomograms of the sella turcica and serum prolactin concentrations were obtained in 146 women with amenorrhea, galactorrhea, or both to diagnose prolactin-secreting pituitary adenomas. Findings suggesting an adenoma, ie, abnormal tomogram and elevated serum prolactin concentration, were found in 24.6% (16/65) of previously unscreened patients and 59.2% (48/81) of prescreened patients. The combination of an abnormal tomogram and elevated prolactin level was relatively specific for an adenoma, as 91% (42/46) of women with these findings who underwent surgery had histologically confirmed tumors. Tumors occurred in women from 15 to 45 years of age, with amenorrhea or galactorrhea ranging from less than six months to more than 20 years in duration. Some women in this series also had obesity, rapid weight loss, polycystic ovarian syndrome, amenorrhea following discontinuance of oral contraceptive use, or emotional stress. ( JAMA 244:1329-1332, 1980)

To test the effect of opiate receptor blockade on hormone release in man, we administered 10 mg naloxone iv to eight normal subjects and compared the results with those found after saline infusion. Naloxone produced a rise in serum cortisol (P < 0.01), LH (P < 0.01), FSH (P < 0.05), and insulin (P < 0.05) levels but did not alter serum GH, PRL, TSH, arginine vasopressin, glucagon, T3, or T4. Naloxon e had no effect on GH levels in two subjects with active acromegaly or on TSH levels i n six subjects with primary hypothyroidism. In dynamic pituitary function testing, naloxone diminished the GH response to arginine (P < 0.05) without altering the PRL response; naloxone augmented the PRL response to TRH (P < 0.025) without affecting the TSH response. Naloxone did not significantly alter GH or PRL response to L-dopa. Naloxone enhanced the increment in serum cortisol induced by the stress of gastroscopy without changing the GH or PRL response. Naloxone increased glucose response areas (P < 0.05) after an iv gl...

A long-acting agonist of gonadotropin-releasing hormone (GnRH-a, 100 micrograms/day) was administered daily for 14 days in four patients with polycystic ovarian disease (PCOD) and eight ovulatory women (OW) to determine acute hormone responses. Initiation of GnRH-a treatment in OW on day 5 of their menstrual cycles (OW-day 5) stimulated a greater acute rise of serum follicle-stimulating hormone (FSH) than that seen in OW beginning treatment on day 2 (OW-day 2) or PCOD patients. FSH levels fell to baseline values with repeated injections, whereas luteinizing hormone levels remained elevated in all patients. An acute rise and progressive fall of estradiol (E2) was found in all groups. The OW-day 5 group demonstrated a secondary increase, which by day 14 was clearly greater than that found in the other groups. This secondary increase of E2 in the OW-day 5 group was associated with lower abdominal pain, whereas OW-day 2 and PCOD patients were asymptomatic. For comparison, human menopausal gonadotropin (150 IU/day for 3 days) stimulated a significantly greater increase of E2 in OW-day 5 than in PCOD patients. These studies indicate that daily GnRH-a administration induced variable effects on ovarian function, which depended on when it was begun during the menstrual cycle and whether it was given to ovulatory or PCOD subjects. In addition, abdominal discomfort associated with GnRH-a use in regularly OW can be avoided by commencing agonist administration earlier in their menstrual cycles.

This study was designed to investigate whether the amounts of progesterone (P) normally present at midcycle, when administered to normal women pretreated with estradiol benzoate (E2B), alter the release of LH and FSH. Twelve subjects (four groups of three) were studied during two menstrual cycles. On day 1 of both the initial (E2 control) and a subsequent (study) cycle, each subject received E2B im (2.5 micrograms/kg/12 h) for a total of seven injections. Twelve hours after the final injection, gonadotropin-releasing hormone (GnRH) was given. In the study cycle, P in oil was added to each of the last three injections of E2B in doses of 1.25 (group I), 2.5 (group II), or 5.0 (group III) mg/12 h, and in one group (IV) in graded doses of 1.25 2.5, and 5.0 mg/12 h. Estradiol levels were similar in both cycles, with a mean (+/- SE) of 271 +/- 3 pg/ml. During the interval of P administration, mean P levels rose gradually from 0.3 +/- 0.02 to 1.3 +/-0.12 ng/ml (mean +/- SE of all groups). In the study cycle, an FSH rise occurred in 8 of 12 subjects, while an LH surge greater than that in the E2 control cycle occurred in all but one subject. Peak levels of these surges usually occurred within 24 h of the initial P injection, which is similar to the relationship between the initial rise of P and the occurrence of peak gonadotropin levels at midcycle in normal women. The mean delta max of FSH and LH in subjects exhibiting gonadotropin rises approximated the magnitude of the gonadotropin increases observed normally at midcycle. In response to GnRH during the study cycle, the magnitude of the FSH rise was augmented in 6 of 12 subjects and of LH in 9 of 12, when compared to the E2 control cycles. These data suggest that P, in the presence of late follicular phase levels of E2, 1) augments the release of LH, 2) may induce the release of FSH, and 3) further modulates pituitary responsiveness to GnRH. The data are consistent with the hypothesis that the rising concentrations of E2 to which the hypothalamic-pituitary system is exposed for an appropriate duration serve to initiate the surge of LH at midcycle. This increased LH in turn, stimulates the production of P, which not only further augments the LH surge but, when coupled with E2, also can effect the midcycle FSH surge.

A prospective study of 46 women with prolactin-secreting pituitary adenomas and amenorrhea and/or galactorrhea was performed to determine the influence of the selective transsphenoidal removal of these tumars on pituitary and reproductive function. This procedure was effective in restoring menstrual function in 34 of 41 women and in eliminating lactation in 30 of 40 women. Tumor size and preoperative serum prolactin concentrations were the most important factors in predicting the postoperative disappearance of symptoms. Normal menstrual function returned in 33 of 34 women with tumors 2 cm. Similarly, galactorrhea disappeared in 29 of 34 women with tumors

To assess the effectiveness of bromocriptine in reducing the size of PRL-secreting macroadenomas with extrasellar extension, we conducted a prospective multicenter trial in patients without prior radiotherapy, applying a standard protocol of treatment and tumor size evaluation. Basal serum PRL levels [1441 +/- 417 (+/- SEM) ng/ml for women; 3451 +/- 1111 ng/ml for men] fell in all patients and to 11% or less of basal values in all patients but 1. Normal PRL levels were reached in 18 of the 27 patients. In 13 patients (46%), tumor size was reduced by greater than 50%, in 5 patients (18%) by about 50%, and in 9 patients (36%) by approximately 10-25%. The extent of tumor size reduction did not correlate with basal PRL, nadir PRL, percent fall in PRL, or whether PRL levels reached normal. However, a reduction in PRL levels always preceded any detectable change in tumor size. In 19 patients, reduction in tumor size was evident by 6 weeks, but in the other 8, such reduction was not noted until the 6 month evaluation. In the 4 patients in whom bromocriptine was discontinued at the end of 1 yr, tumor reexpansion occurred in 3. Visual fields improved in 9 of the 10 patients in whom they were abnormal. Because of the excellent results found in most of the patients in this series, we suggest that therapy with bromocriptine should be considered as initial management for patients with PRL-secreting macroadenomas.

The glandular origin of excess circulating steroid hormones in women with polycystic ovarian disease has been difficult to establish with previously described perturbation techniques. Recently it was demonstrated that daily administration of a potent gonadotropin-releasing hormone agonist achieves complete and reversible suppression of ovarian steroid secretion. To examine the source of C-21 steroid hormones, circulating levels were measured before and after administration of the same agonist in polycystic ovarian disease subjects and normal control subjects. Serum levels of these hormones were also determined after administration of dexamethasone and adrenocorticotropic hormone (ACTH) as well as bilateral oophorectomy. Subjects with polycystic ovarian disease exhibited significant elevations of serum pregnenolone, 17OH -pregnenolone, and 17OH -progesterone by comparison with normal control subjects. The glandular origins of the excess levels of pregnenolone and 17OH -pregnenolone were more difficult to determine and appear to be different from that of 17OH -progesterone.

Immunologic infertility is an important area of current clinical research. The immunobead test is a laboratory method that identifies the classes of antisperm antibodies and their binding sites on the sperm surface. In this study we have investigated the variability in the pattern of antibody binding to spermatozoa after passive transfer from blood serum. Serum from a single donor containing antisperm antibodies of the IgG class was used in all experiments. The spermatozoa from 27 semen donors were found to differ significantly in the degree and location of immunobead binding after exposure to this serum. There was substantial day-to-day variability in the results for individual semen donors and the overall variability in test results was significantly greater when a number of semen donors was used rather than a single donor. These data suggest that details of antisperm antibody binding after passive transfer from body fluids may depend on the sperm donor. The design of research studies involving antibody transfer must take this source of variability into account.

Previously, we reported that short term administration of a highly potent GnRH agonist (GnRHa) for 1 month to patients with polycystic ovarian disease (PCO) resulted in complete suppression of ovarian steroidogenesis without measurable effects on adrenal steroid production. This new study was designed to evaluate the effects of long term GnRHa administration in PCO patients with respect to their hormone secretion patterns and clinical responses. Eight PCO patients and 10 ovulatory women with endometriosis were treated daily with sc injections of [D-His6-(imBzl]),Pro9-NEt]GnRH (GnRHa; 100 micrograms) for 6 months. Their results were compared to hormone values in 8 women who had undergone bilateral oophorectomies. In response to GnRHa, PCO and ovulatory women had rises of serum LH at 1 month, after which it gradually declined to baseline. In both groups FSH secretion was suppressed throughout treatment. Serum estradiol, estrone, progesterone, 17-hydroxyprogesterone, androstenedione, and testosterone levels markedly decreased to values found in oophorectomized women by 1 month and remained low thereafter. In contrast, serum pregnenolone and 17-hydroxypregnenolone were partially suppressed, and dehydroepiandrosterone, dehydroepiandrosterone sulfate, and cortisol levels did not change. Clinically, hyperplastic endometrial histology in three PCO patients reverted to an inactive pattern, and proliferative endometrium in two other PCO patients became inactive in one and did not change in the other. Regression of proliferative endometrial histology occurred in all ovulatory women. Vaginal bleeding occurred in all women studied during the first month of GnRHa administration, after which all but one PCO patient became amenorrheic. Hot flashes were noted by all ovulatory women and by four of eight PCO patients. All PCO patients noted subjective reduction of skin oiliness, and five had decreased hair growth. We conclude that in premenopausal women: 1) chronic GnRHa administration results in apparently complete persistent suppression of ovarian steroid secretion; 2) adrenal steroid secretion is not influenced directly or indirectly; and 3) its use may be helpful in the treatment of endometrial hyperplasia and ovarian androgen excess in women with PCO.

The principal glandular source of increased serum androgens in polycystic ovarian disease (PCO) is controversial), since complete separation of ovarian from adrenal function has not been achieved. The purpose of this study was to determine whether a long-acting GnRH agonist could be used to selectively inhibit ovarian steroid secretion in PCO and ovulatory women. Each of five typical PCO patients and six ovulatory subjects on day 2 of their menstrual cycles received D-Trp6-Pro9-NEt-LHRH (GnRH-a; 100 micrograms) for 28 consecutive days. Their results were compared to basal serum hormone values in eight oophorectomized women. In response to GnRH-a, PCO and normal subjects exhibited sharp and sustained rises of LH and gradual decreases in FSH. These levels were clearly less than basal levels seen in oophorectomized women. Episodic LH release was significantly attenuated in both groups at the end of GnRH-a treatment. After the administration of agonist, serum estradiol (E2), estrone (E1), androstenedione (A), and testosterone (T) were suppressed to castrate levels in both groups. The decrements of E2 and E1 in PCO were gradual and continuous compared to initial dramatic rises, which reached peaks at 14 days, and subsequent abrupt falls in the ovulatory controls. Serum A and T declined steadily in both groups. Basal serum dehydroepiandrosterone and dehydroepiandrosterone sulfate, but not cortisol, levels were elevated in PCO subjects. The 24-h secretion patterns and responses to ACTH of these hormones in PCO and ovulatory subjects were unaltered by GnRH-a administration. These data demonstrate that 1) in PCO subjects, GnRH-a induced complete suppression of ovarian steroid secretion, as circulating levels at the end of treatment were comparable to those seen in our oophorectomy subjects; 2) elevated A and T levels in PCO patients were derived primarily from the ovary; and 3) adrenal steroid secretion was unaltered by GnRH-a in both PCO and normal women.

A 31-year-old nulligravid patient presented with irregular menses, severe hirsutism, and infertility. Evaluation revealed marked increases of serum androstenedione and testosterone levels and a possible ovarian mass. At operation a cystic teratoma was removed from the left ovary and bilateral wedge resection revealed severe ovarian hyperthecosis. After operation only a transient decrease of androstenedione and testosterone was noted and the patient failed to ovulate or improve clinically. Subsequently a long-acting gonadotropin-releasing hormone agonist was administered daily for 6 months, which reduced circulating delta 4-steroids and estrogens to levels approximating those of castrated women. Immediately after discontinuation of treatment, ovulation induction was successfully achieved with human menopausal gonadotropin. This report introduces a new therapeutic approach to the problem of severe ovarian hyperthecosis and may provide an opportunity for childbearing in these patients.

This paper describes an architecture for the control of robotic devices, and in particular of anthropomorphic hands, characterized by a hierarchical structure in which every level of the architecture contains data and control function with varying degree of abstraction. Bottom levels of the hierarchy interface directly with sensors and actuators, and process raw data and motor commands. Higher levels perform more symbolic types of tasks, such as application of Boolean rules and general planning operations. The implementation of the layer has to be consistent with the type of operation and its requirements for real time control. One implementation of the rule level, with a Boolean artificial neural network which would have a response time sufficient for producing reflex corrective action at the actuator level is presented.

CV 205-502 is a nonergot oral dopamine agonist with specific D2 activity, which has a prolonged suppressive effect on serum PRL and may have fewer side-effects than other dopamine agonists. We treated 26 hyperprolactinemic women with this compound given as a single bedtime (hs) dose for up to 12 weeks. All had gonadal dysfunction, either amenorrhea or oligomenorrhea, and 15 had galactorrhea. The initial and subsequent doses were administered in a randomized fashion; the initial dose ranged from 0.01-0.05 mg, and the dose at 12 weeks ranged from 0.03-0.09 mg. The women were evaluated every 2 weeks, and the dose was increased by 0.02 mg every 4 weeks if the serum PRL level was greater than 20 micrograms/L. Of the 26 women initially enrolled, 24 completed 12 weeks of therapy, and 2 discontinued therapy because of side-effects. Thirteen women (54%) had return of menses, and 12 (80%) had either a decrease in or disappearance of galactorrhea. Serum PRL concentrations decreased to a variable degree in all patients; 13 (54%) achieved a normal serum PRL level (less than or equal to 20 micrograms/L). The mean (+/- SE) pretreatment serum PRL concentration was 129 +/- 34, and it was 29.9 +/- 5.9 micrograms/L after 12 weeks of treatment (P = 0.005). The mean (+/- SE) percent reduction in serum PRL was 66.5 +/- 5.0% (median, 78.0%). A dose response was not demonstrated (r = -0.08; P = 0.70) among the 6 dose groups during the last 4 weeks of therapy. In 5 women, serum PRL levels, measured frequently for 24 h after treatment remained low. Side-effects after the initiation of therapy included nausea, headache, and morning fatigue in 10 women. These symptoms caused 2 women to discontinue therapy; they subsided in the other women. An optimal dose was not determined and will probably need to be determined by titration in each patient. CV 205-502, given once daily, appears to be a safe and effective alternative to other dopamine agonists in the treatment of hyperprolactinemia.

Macroglobulin rheumatoid factors have been detected in the sera of howler monkeys ( A. caraya ). These IgM antibodies cross-reacted with human and rabbit IgG. Additional IgM auto-antibodies were identified in the same sera together with an abnormal protein component. Maintenance in captivity was associated with a disappearance of both the autoantibodies and the abnormal serum protein. These serologic findings and IgM autoantibodies were likely due to a pigmentary deposit in the liver. This disorder previously detected was considered to be secondary to intense stimulation of the reticuloendo-thelial system by an exogenous (infectious?) environmental agent.

Three hypogonadotropic female siblings, aged 19, 19 (twins), and 22 yr, with primary amenorrhea, lack of secondary sexual development, and retinitis pigmentosa were evaluated to determine hypothalamic-pituitary-ovarian function and anterior pituitary hormone release. Spontaneous LH, FSH, PRL, TSH, GH, cortisol (F), dehydroepiandrosterone (DHEA), and DHEA sulfate (DHEA-S) secretory patterns were determined by assay of hourly blood samples obtained over a 24-h period. Studies of stimulated release of anterior pituitary hormones included: gonadotropin response to LRF (two 10 µg iv pulses at 2-h intervals) before and after 1) estradiol benzoate (5 µg/kg- 12 h, im for 5 days) and 2) repetitive low dose LRF (0.025 µg/kg. 2 h, iv for 5 days); PRL and TSH responses to TRH (500 µg iv bolus); and GH and F responses to an insulin tolerance test (0.1 U/kg). Ethinyl estradiol (50 µg/day, orally) was administered for 4 weeks, after which endocrine evaluation was repeated. The mean basal levels of LH and FSH were simila...

The disassociation between serum LH and FSH levels in polycystic ovarian disease (PCO) has been attributed to chronic acyclic estrogen production characterized by a predominance of circulating estrone (E1). This study was designed to determine whether the administration of estrone benzoate (E1B) modulates gonadotropin release in PCO. In five normal women studied during the early follicular phase of a control and subsequent treatment cycle, daily LH and FSH levels were unaltered by E1B administered from days 2 to 6. Gonadotropin responses to LRF given on day 7 were similar during control and treatment cycles. In seven patients with PCO, the mean LH concentration (25.7 +/- 0.7 mIU/ml) and the daily pattern of release were unchanged by E1B administered for 14 days. In contrast, a progressive decline in FSH occurred in each subject. Mean FSH levels decreased significantly from a pretreatment value of 11.3 +/- 0.2 to 9.3 +/- 0.9 mIU/ml by day 2 (P less than 0.05) and 7.2 +/- 1.2 mIU/ml by day 14 (P less than 0.005) of E1B administration. The LH response to LRF in PCO was significantly greater than that observed in the normal subjects, whereas responses before, during, and after E1B administration were similar. The FSH responses to LRF in PCO subjects were comparable to those of the normal subjects. These data indicate that the administration of E1B to PCO subjects reduces FSH levels without altering LH release, thereby enhancing the disparity of gonadotropin secretion encountered in this syndrome. This finding is consistent with the hypothesis that impairment of FSH release by chronic acyclic estrogen production derived from nonglandular aromatization of circulating androgen could in large part be responsible for anovulation in PCO.

We hope that this article brings into focus some problems that merit consideration and debate. These thoughts come from a group of individuals who are actively engaged in reproductive endocrine/infertility practices with special interests ranging from ovulation induction to IVF to laser surgery. As a group, we practice in all parts of the country, and the problems mentioned are not restricted to any individual or region. We urge that all of us be candid with ourselves and our colleagues about what we can and cannot do for the infertile couple. We suggest that gynecologists ask themselves this question and proceed when the answer is affirmative: "Is this procedure really in the patient's best interest?"

The authors have developed an extension of the sperm penetration assay for detecting serum immunoglobulins to sperm antigens that are transferred to the plasma membrane of a sperm-penetrated hamster oocyte. After the hamster oocytes have been scored for sperm penetration by observing for the presence of swollen sperm heads, they are incubated in serum followed by either a 20-minute treatment with rhodamine-conjugated protein A (which binds to most subclasses of IgA, IgG, and IgM) or a 2-hour incubation in guinea pig serum (complement). Positive fluorescence indicates that the serum contains antibodies to sperm antigens that were transferred to the surface of an oocyte during gamete fusion. Complement-mediated lysis indicates that the immunoglobulin that is bound can also fix complement. The advantages of this assay for detection of serum antisperm antibodies are that it (1) is an extension of a widely used assay, (2) is rapid and requires readily available reagents and equipment, (3) can detect most subclasses of IgA, IgG, and IgM, (4) detects antibodies to those sperm antigens that may be transferred to the oocyte during fertilization, and (5) indicates whether the detected antisperm antibodies can mediate complement-dependent lysis of the fertilized oocyte.

Administration of chlorpromazine-HCI at 5 to 15 mg/kg bodyweight to pregnant CD-1 mice at 24 h after human chorionic gonadotropin (hCG) (20–23 h after mating) inhibited blastocyst formation and reduced the cell number of embryos recovered at 95 h after hCG. When embryos are recovered at the two- to four-cell stage (48–50 h after hCG) and cultured for an additional 47 h (to 95 h after hCG) or 72 h (to 120 h after hCG), blastocyst formation and embryo cell number were similarly reduced. When the dose range was reduced to 0.5 to 2 mg/kg bodyweight, no significant effect of the drug was observed on blastocyst formation or on embryo cell number. However, when aggregation chimeras were formed between embryos recovered from drug-exposed females and from untreated females, a decrease in cell proliferation rate of the embryo from the drug-exposed female was observed at a dose of 2 mg/kg bodyweight. This result indicates that exposing pregnant mice to chlorpromazine-HCI at doses as low as 2 mg/kg bodyweight can induce a potential for decreased cleavage rate in their pre-implantation embryos that can be revealed by challenging those embryos by direct contact with embryos from nonexposed females. Finally, when four-cell stage embryos recovered from untreated females cultured in the presence of chlorpromazine (0.1–25 mM), blastocyst formation and embryo cell number were significantly reduced in a dose-dependent manner. This last result suggests that in vivo the drug may act directly on the embryo from the pronuclear stage to the early morula stage of development.

Excessive adrenal androgen production contributes to hyperandrogenism in polycystic ovarian disease (PCO). This study was performed to determine the concentration of basal plasma ACTH in PCO patients and normal women and correlate its level with that of circulating adrenal androgen. In PCO patients, significant increases in serum testosterone, androstenedione, and dehydroepiandrosterone sulfate were noted compared to levels in normal women. The mean circulating plasma ACTH in PCO patients (22 +/- 2 pg/ml) was not different from that in normal controls (20 +/- 2 pg/ml). The mean ratio of dehydroepiandrosterone sulfate to ACTH in individual PCO patients was significantly greater than that in normal subjects, whereas the cortisol to ACTH ratio was similar in both groups. These results suggest that increased adrenal androgen production in PCO patients is not due to abnormal ACTH secretion but arises from either altered adrenal responsiveness to ACTH or abnormal adrenal stimulation by a factor(s) other than ACTH.

An analysis of anterior pituitary function with respect to abnormal or normal serum prolactin (hPRL) concentrations (normal

Gonadotroph responsivity was evaluated in 33 women with amenorrhea and/or galactorrhea, hyperprolactine-mia, and PRL-secreting pituitary adenomas by testing with GnRH, using three different dosage schedules. The first group received a 100-eg iv bolus of GnRH to evokea maximal gonad-otropin response. The second group received a constant 4-h iv infusion of GnRH(25 eg/h) to assess both gonadotroph sensitivity or readily releasable LH and FSH,and gonadotroph reserve capacity. The third group was given four, submaximal, intermittent, iv doses of GnRH (2.5, 5, 10, and 25 eg) at 2-h intervals to assess both gonadotroph sensitivity and reserve capacity when tested with pulsatile GnRH at concentrations that more closely approximate physiological levels. After the 100-eg bolus of GnRH, the mean ± SE maximal increase in serum LH (A maxLH) and FSH (Δ max FSH) in women with tumors (Δ max LH = 67.8 ± 7.7 mlU/ml;Δ max FSH = 17.2 ± 1.8 mlU/ml) was significantly greater (P < 0.01) than in the control group (Δ max LH = 38....

We have developed a short-term in vitro assay for the detection of sublethal effects produced by very low levels of ionizing radiation. The assay utilizes mouse embryo aggregation chimeras consisting of one irradiated embryo paired with an unirradiated embryo whose blastomeres have been labeled with fluorescein isothiocyanate (FITC). X irradiation (from 0.05 to 2 Gy) and chimera construction were performed with four-cell stage embryos, and the chimeras were cultured for 40 h to the morula stage. The morulae were partially dissociated with calcium-free culture medium and viewed under phase contrast and epifluorescence microscopy to obtain total embryo cell number and the cellular contribution of irradiated (unlabeled) and control (FITC labeled) embryos per chimera. In chimeras where neither embryo was irradiated, the ratio of the unlabeled blastomeres to the total number of blastomeres per chimera embryo was 0.50 (17.8 +/- 5.6 cells per unlabeled embryo and 17.4 +/- 5.5 cells per FITC-labeled partner embryo). However, in chimeras formed after the unlabeled embryos were irradiated with as little as 0.05 Gy, the ratio of unlabeled blastomeres to the total number of blastomeres per chimera embryo was 0.43 (P less than 0.01). The apparent decreases in cell proliferation were not observed in irradiated embryos that were merely cocultured with control embryos, regardless of whether the embryos were zona enclosed or zona free. We conclude that very low levels of radiation induce sublethal changes in cleaving embryos that are expressed as a proliferative disadvantage within two cell cycles when irradiated embryos are in direct cell-to-cell contact with unirradiated embryos.