Laparoscopic hemi-hysterectomy in treatment of a didelphic uterus with a hypoplastic cervix and obstructed hemi-vagina.

OBJECTIVE: Maldevelopment of the Müllerian duct system may result in various urogenital anomalies including didelphic uterus with a hypoplastic cervix and obstructed hemi-vagina. CASE REPORT: We report a patient with this anomaly who was treated by laparoscopic hemi-hysterectomy and hysteroscopic resection of hemi-vagina. A 16-year-old patient who had complained of vaginal pus-like discharge on and off for 1 year was diagnosed by MRI to have a double uterus with obstructed right hemi-vagina and ipsilateral renal agenesis. After hysteroscopic identification of hypoplasia of the right uterine cervix, laparoscopic resection of the right uterus and right fallopian tube and hysteroscopic assisted resection of the vaginal septa were performed successfully. CONCLUSION: We think that combined laparoscopy and hysteroscopy may be an effective alternative in the management and diagnosis of Mullerian anomalies.

Preparing for an influenza pandemic in Italy: resources and procedures in paediatric hospital units.

The World Health Organization (WHO) has stated that preparedness for effectively facing a major influenza epidemic should involve the training of physicians in the management of contagious diseases and upgrading hospital resources and procedures [1]. Children would be particularly vulnerable during an influenza pandemic and specific measures are needed to face the threat to them effectively. We performed a national survey to obtain information about the preparedness in facing a major influenza outbreak in Italian paediatric units. In Italy, paediatrics clinics are found in both paediatric wards and paediatric departments. Departments are more complex structures, containing several units with different specialisations and facilities. For this study, we interviewed heads of both departments and units. A structured questionnaire, including 30 items, was submitted to the heads of 150 paediatric hospital departments across the country. Responses were obtained from 123 units; 10% of these had rooms dedicated to infectious diseases, and 4% had experts in infectious diseases available and routinely applied procedures for preventing the spreading of acute infectious diseases. Only 8% of departments have paediatric intensive care facilities. Few paediatric units, usually located in large children's hospitals or in academic paediatric departments, have a sufficient degree of preparedness to face severe influenza pandemics. A structural improvement of the paediatric units and the use specific procedures are essential for effectively care for children hospitalised because of contagious diseases.

Calcium antagonists and hormone release. II. Effects of verapamil on basal, gonadotropin-releasing hormone- and thyrotropin-releasing hormone-induced pituitary hormone release in normal subjects.

Although it has been well established that Ca2+ plays an essential role in the release of several hormones, very little is known of the interactions between Ca2+ and secretagogues in the process of pituitary hormone release. One possible way of studying the mechanism of action of hypothalamic releasing hormones is to study how organic calcium antagonists affect their action. Consequently, we infused the commonly used calcium antagonist, verapamil, into 20 normal subjects (10 men and 10 women; aged 19-37 yr) and studied its effects on both basal pituitary hormone levels and augmented hormonal release induced by gonadotropin-releasing hormone (GnRH) and TRH. Verapamil, infused at a rate of 5 mg/h for 3 h, induced a significant and marked suppression of circulating LH and FSH levels in both men and women. By the end of the infusion, the suppression of release was greater for LH (60%) than for FSH (54%). After the termination of the infusion, plasma gonadotropin concentrations returned progressively to basal levels within 2 h. Verapamil was also capable of blunting the peak incremental gonadotropin response to GnRH. Although the basal TSH concentration was apparently unaffected by verapamil, the incremental TSH response to TRH was significantly inhibited in both men and women. Verapamil infusion did not affect either the basal PRL concentration or the PRL response to TRH. Our data provide evidence that verapamil exerts different effects on the release of pituitary hormones in normal subjects. It inhibits the centrally mediated as well as the peripherally mediated gonadotropin release and blunts the TSH response to TRH. On the contrary, verapamil does not seem to affect basal or TRH-mediated PRl release. The use of organic calcium antagonists in experimental models in vitro as well as in vivo appears to offer a promising tool for further studies on the mechanism of action of secretagogues in the process of hormone release.

Thyroidal accumulation of 131I during adrenal gland scintigraphy with 131I-19-iodocholesterol: effects of thyroid blocking agents.

131I-19-iodocholesterol has been used by Beierwaltes et al., to visualize human adrenal glands. The tissue distribution of 131I-19-iodocholesterol was determined by Morita et al., both in dogs and men. No data have been reported on thyroidal 131I accumulation after administration of the radiopharmaceutical. We calculated the percentage uptake of radioactivity in the human thyroid gland inhibited with various therapeutic agents (triiodothyronine (T3), Lugol's solution, potassium perchlorate (KC1O4).

Serum prolactin response to thyrotropin-releasing hormone and metoclopramide in patients with prolactin-secreting tumors before and after transsphenoidal surgery.

Seven female patients with amenorrhea, galactorrhea, and hyperprolactinemia were examined before and after selective transsphenoidal removal of a PRL-secreting microadenoma. Before adenomectomy, metoclopramide (MCP; 10 mg orally) and TRH (200 micrograms iv) did not increase PRL blood levels in any of the seven patients. On the contrary, after oral administration of 10 mg MCP, a positive response was noted in a group of eight lactating women 3 days postpartum. After surgery, serum PRL level returned to normal in all patients. A positive PRL response to MCP and TRH was found in six of the seven patients 1 month after surgery. One patient, who had the lowest PRL level, failed to show a PRL increase after both stimuli. These findings indicate that hypothalamic pituitary function can be restored to normal after transsphenoidal removal of PRL-secreting pituitary tumors.

Estrogen-dependent plasma prolactin response to gonadotropin-releasing hormone in intact and castrated men.

Although it has been recently shown that GnRH is capable of increasing plasma PRL levels in humans, the role played by the steroid hormone environment in influencing this response has not been clarified. Fourteen intact and 14 castrated subjects with carcinoma of the prostate were studied before and after daily treatment with 1.5 mg estradiol benzoate (E2B), im, for 9 days PRL responsiveness was tested after GnRH was given as an iv bolus or a continuous infusion for 4 h. During a 4-h saline infusion after E2B treatment, plasma PRL levels were measured in 8 intact and 8 castrated subjects for control purposes. No significant increase in PRL levels was noted after iv bolus or infusion of GnRH in intact or castrated men. After the administration of pharmacological doses of E2B for 9 days, plasma PRL levels increased significantly in all subjects after both the iv bolus and the infusion of GnRH. During saline infusion, a significant decrease in plasma PRL levels was observed in all subjects. Plasma gonadotropin levels showed the expected increase after GnRH administration. Our findings confirm that GnRH is one of the numerous substances capable of stimulating PRL release in humans and demonstrate that in men: 1) pharmacological doses of estrogen induce a PRL response to GnRH, and 2) GnRH elicits different patterns of PRL release depending on the modality of administration. Finally, the physiological role of GnRH in PRL release, if any, remains to be established.

Postoperative evaluation of dopaminergic tone in prolactinoma patients. II. Plasma thyrotropin response to metoclopramide.

In 24 patients who had a PRL-secreting pituitary adenoma, diagnosed by pituitary dynamic function tests and CT scan, and confirmed at surgery, the TSH response to a dopamine (DA)-antagonist drug, metoclopramide (MCP), was studied pre- and postoperatively to elucidate whether altered DA tone was present and related to hyperprolactinemia. Preoperatively, a TSH response to MCP occurred in 18 patients. Plasma TSH levels did not increase after MCP in 5 patients who had a macroprolactinoma and in 1 patient with a microprolactinoma located just beneath the diaphragm of the sella turcica. Postoperatively, in all patients who had a prolonged clinical remission and normalization of PRL dynamic tests TSH did not respond to MCP (9 of 24 patients). In 4 patients who had normal or borderline PRL levels in the immediate postoperative period, the TSH response to MCP disappeared, but became evident later together with progressive elevation of PRL levels. TSH increases after MCP occurred in all patients who had abnormal PRL levels after surgery, except in 2 patients with a macroprolactinoma infiltrating the neighboring structures. In conclusion, these results confirm the existence of increased DA tone in patients with a prolactinoma. However, the presence of an increased TSH response to DA antagonist drugs could be masked in patients who had large tumors or tumors located just beneath the sellar diaphragm. The TSH test after MCP administration can readily detect increased DA tone in the postoperative period even when PRL levels remain slightly elevated or borderline.

Corticotropin-releasing hormone inhibition of growth hormone-releasing hormone-induced growth hormone release in man.

Recent studies in the rat have shown that intracerebroventricular administration of CRH inhibited spontaneous pulsatile GH secretion and prevented GH-releasing hormone (GHRH)-induced GH release. We have studied the effect of CRH on GHRH-induced GH release in man. In the first study, CRH was injected iv at three different doses (100, 50, or 25 micrograms) at 0800 h together with 50 micrograms GHRH in six men and six women. In a second study, 100 micrograms CRH were given iv at 0800 h, 1 h before the administration of 50 micrograms GHRH in five men and five women. Each subject demonstrated a normal GH response after the administration of 50 micrograms GHRH plus saline. All doses of CRH administered simultaneously with GHRH significantly inhibited GHRH-induced GH release in women [peak value +/- SE after GHRH plus saline, 28.9 +/- 2.9 micrograms/L; after GHRH plus 100 micrograms CRH, 9.9 +/- 0.7 micrograms/L (P less than 0.001); after GHRH plus 50 micrograms CRH, 8.7 +/- 0.8 micrograms/L (P less than 0.001); after GHRH plus 25 microgram CRH, 9.5 +/- 1.6 microgram/L (P less than 0.001]). In contrast, in men, while a dose of 100 micrograms CRH was capable of suppressing GHRH-induced GH secretion (peak value +/- SE, 8.1 +/- 0.6 vs. 20 +/- 2.9 micrograms/L; P less than 0.001), no inhibition was observed after 50- and 25-micrograms doses. When 100 micrograms CRH were injected 1 h before the administration of 50 micrograms GHRH, it strongly inhibited GHRH-induced GH secretion in both men (peak value +/- SE, 6.2 +/- 2.8 vs. 24.6 +/- 5.9 micrograms/L; P less than 0.02) and women (peak value +/- SE, 14.2 +/- 4.5 vs. 37.8 +/- 6.7 micrograms/L; P less than 0.005), and this inhibition lasted up to 2 h post-CRH administration. These results demonstrate that CRH is capable of inhibiting GHRH-induced GH release in both men and women. Furthermore, the findings suggest that a sexual dimorphism in the neuroregulation of GH secretion may be present in man. In view of the inhibitory action of CRH on GH secretion, simultaneous administration of CRH and GHRH for testing should be avoided in clinical practice.

Differential effects of feeding on the ultradian variation of the growth hormone (GH) response to GH-releasing hormone in normal subjects and patients with obesity and anorexia nervosa.

Nutritional status and metabolic fuels are factors involved in the regulation of GH secretion and GH responses to GHRH. The effects of feeding on GHRH-induced GH release were studied in 13 normal women, 14 obese women, and 9 women with anorexia nervosa. GHRH-(1-44) (50 micrograms, iv) was administered at 0900 h after an overnight fast or at 1300 h after a normal meal at 0800 h, and at the same times 45 min after a 800-Cal meal on different days. The mean peak plasma GH responses to GHRH administered before a meal at 0900 h were 52.8 +/- 5.6 (+/- SE) micrograms/L in normal women, 8.2 +/- 1.3 micrograms/L in obese women, and 53.2 +/- 7.7 micrograms/L in anorexic women. When GHRH was administered before a meal at 1300 h, the mean peak plasma GH levels were lower than those at 0900 h; this reduction was -64.2% in normal women, -64.9% in obese women, and -55.8% in women with anorexia nervosa. After feeding, the plasma GH responses to GHRH were blunted in normal women at 0900 h (-60.9%) and 1300 h (-34.6%) compared with the fasting peak responses. In obese women the plasma GH response to GHRH after feeding was increased compared with that when these women had fasted (+60% at 0900 h and +406.9% at 1300 h). Finally, differential effects of feeding were present in anorexic women; the response was lower at 0900 h (-46.4%) and greater at 1300 h (+50.8%). We conclude that there is an ultradian variation in GHRH-stimulated GH secretion and that the responses differ according to nutritional status and body weight.

Treatment of hyperthyroidism due to inappropriate secretion of thyrotropin with the somatostatin analog SMS 201-995.

The management of hyperthyroidism due to inappropriate secretion of TSH (IST) includes agents that selectively suppress TSH hypersecretion both in patients with TSH-secreting tumor [neoplastic IST (nIST)] in whom pituitary surgery was unsuccessful and in those with selective pituitary resistance to thyroid hormone action [nonneoplastic IST (nnIST)]. Among such agents, somatostatin administration has proven to be effective in blocking TSH hypersecretion, but its short plasma half-life prevented its use in long term therapeutic trials. The recent availability of a potent and long-acting analog of somatostatin (SMS 201-995, Sandostatin) prompted us to study its effects on serum TSH, alpha-subunit, and free thyroid hormone (FT4 and FT3) concentrations in five patients with nIST and three patients with nnIST. During short term SMS 201-995 administration (100 micrograms, sc, three times daily for 5 days) both serum TSH and alpha-subunit levels decreased in all patients with nIST (mean decrements, -86% and -85%, respectively), with concomitant normalization of serum FT4 and FT3 concentrations. In the three patients with nnIST, this treatment lowered serum TSH levels less well (mean decrement, -47%), although serum FT4 and FT3 levels normalized in one patient. Chronic SMS 201-995 (100 micrograms, sc, every 12 h for 1-7 months) treatment in four hyperthyroid patients (two with nIST and two with nnIST) resulted in a steady euthyroid state in both patients with nIST, with restoration of normal visual fields in one patient. In contrast, in both patients with nnIST, escape occurred after 2 weeks of therapy. We conclude that SMS 201-995 administration is effective treatment for patients with nIST, able to suppress TSH hypersecretion from the adenomatous thyrotrophs and, consequently, to restore clinical and biochemical euthyroidism in such patients. On the contrary, the inhibitory effects of SMS 201-995 on TSH secretion in patients with nnIST are weaker and transient.

Corticotropin-releasing hormone inhibition of gonadotropin release and the effect of opioid blockade.

We studied the inhibitory effect of exogenous CRH on pulsatile gonadotropin secretion and the role of endogenous opioid peptides in this phenomenon in normal women. To do so, we infused human CRH (100 micrograms/h for 3 h) into 15 normal women during the midluteal phase of their menstrual cycle and studied its effect on both basal (10 women) and GnRH-stimulated (5 women) plasma gonadotropin levels. CRH infusion induced a significant decrease in plasma LH and FSH levels in all women. The decline in plasma LH (62%) was greater than that in FSH (36%). Plasma LH and FSH concentrations returned to basal levels within 30 min after the end of the CRH infusion. CRH infusion did not alter the gonadotropin response to GnRH. We also infused naloxone plus CRH in the 10 women who had received CRH alone during the midluteal phase of a different cycle. Addition of naloxone to CRH (5 women) reversed the LH and FSH inhibition when naloxone was started 1 h after the start of the CRH infusion. When naloxone was started 1 h before CRH infusion (5 women), plasma LH and FSH concentrations did not change. Plasma cortisol increased similarly during both the CRH and CRH plus naloxone infusions; the mean cortisol levels at the end of the CRH and CRH plus naloxone infusions were 497 +/- 40 (+/- SE) and 484 +/- 41 nmol/L, respectively, compared to 240 +/- 14 nmol/L after saline infusion (P less than 0.001). These results demonstrate that in normal women during the midluteal phase of the menstrual cycle, CRH inhibits the secretion of both LH and FSH. The CRH-induced inhibition of gonadotropin secretion is primarily mediated by endogenous opioid peptides, and this effect is not dependent on glucocorticoid levels. We suggest that the disruptive effect of stress on reproductive function in the women could be, at least in part, dependent on decreased gonadotropin secretion induced by elevated endogenous CRH levels.

Sexual dimorphism of pyridostigmine potentiation of growth hormone (GH)-releasing hormone-induced GH release in humans.

Sex differences in the neuroregulation of GH secretion are not now known in humans. To investigate whether activation of cholinergic tone by pyridostigmine could cause a sex-related difference in the pituitary responsiveness to GH-releasing hormone (GHRH), we have studied the GH response to GHRH in 16 normal subjects (8 men and 8 women) tested after oral placebo or different doses of pyridostigmine (30, 60, and 120 mg). Each subject presented a normal response after iv administration of 50 micrograms GHRH and placebo. In men each dose of pyridostigmine induced a significant increase in the GH response to GHRH, as assessed by both the maximal GH peak and the area under GH curve. In women, on the contrary, the GH response to GHRH was not potentiated by pretreatment with pyridostigmine at any given dose. Only five female subjects were tested with 120 mg pyridostigmine because of the severe side-effects of the drug at this dosage. Our present data strongly suggest that in humans there is a sex-related difference in the neuroregulation of GH secretion and this is probably expressed through a different cholinergic tone.

Dexamethasone inhibition of interferon-alpha 2-induced stimulation of cortisol and growth hormone secretion in chronic myeloproliferative syndrome.

This study investigated the acute effects of interferon-alpha 2 (IFN-alpha 2) on hormonal secretion in adult patients affected by a chronic myeloproliferative syndrome and tried to shed some light on the mechanism by which IFN-alpha 2 stimulates cortisol and GH secretion in humans. We compared the pattern of IFN-alpha 2-induced cortisol and GH release with that elicited after the same challenge given subsequent to pretreatment with dexamethasone (Dex). We studied eight patients affected by a chronic myeloproliferative syndrome (thrombocythemia) who had been selected for treatment with IFN-alpha 2. Four sets of experiments were performed: 1) 2 mL iv saline was given at 0800 h in eight cases; 2) 3 x 10(6) IU iv IFN-alpha 2 was given at 0800 h in eight cases; 3) 3 x 10(6) IU iv IFN-alpha 2 was given at 0800 h after pretreatment with 1.5 mg Dex (1 mg at midnight the previous night and 0.5 mg at 0700 h on the day of the test) in six cases; and 4) 2 mL iv saline was given at 0800 h after the same Dex pretreatment in four cases. Cortisol and GH were measured in plasma samples drawn at 30-min intervals between 0800 and 1300 h. Acute iv administration of IFN-alpha 2 stimulated the release of both cortisol and GH in each patient with a significant increment vs. control values, as assessed by areas under the curve. The administration of Dex significantly decreased basal plasma cortisol secretion and abolished cortisol response to IFN-alpha 2 administration. These data suggest that the stimulatory action of IFN-alpha 2 on cortisol release is mediated via a modulation of the activity of the hypothalamic-pituitary axis rather than through a direct effect at the level of the adrenal cortex. After Dex plus saline administration, no significant effect was observed on plasma GH levels, which remained low. Dex administration significantly decreased GH response to IFN-alpha 2. These data suggest that a hypothalamic or pituitary stimulation (or both) is involved in the mechanism of IFN-alpha 2-induced GH secretion. It remains to be established whether IFN-alpha 2 directly stimulates pituitary somatotropic cells or whether the cytokine exerts a stimulatory action on GH secretion by indirectly modulating the hypothalamic or pituitary activity. In conclusion, acute iv administration of IFN-alpha 2 represents a potent stimulus for cortisol and GH secretion in adult human subjects.(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of acute and chronic administration of tamoxifen on GH response to GHRH and on IGF-I serum levels in women with breast cancer.

Tamoxifen, an estrogen antagonist, is usually employed in the treatment of breast cancer. Its mechanism of action is not well known because an antiproliferative effect of the drug has been shown also in estrogen receptor negative tumors, most likely mediated by the inhibition of local growth factors and particularly IGF-I. However, the action of tamoxifen on the GH-IGF-I axis is still open to investigation. We have investigated the influence of acute and chronic treatment with tamoxifen on GH response to GHRH and IGF-I serum levels in six postmenopausal women with metastatic breast cancer. A GHRH test (50 microg i.v. at time 0, GH determinations at 0, 15, 30, 60, 90 and 120 min) was performed (a) basally, (b) 3 h after 40 mg oral administration of tamoxifen and (c) after 8 weeks of 20 mg twice a day oral tamoxifen treatment. IGF-I was measured basally and after chronic tamoxifen therapy. No significant modifications in GH response to GHRH were observed after acute or chronic treatment with tamoxifen vs the basal test. On the contrary, chronic tamoxifen treatment induced a significant decrease in serum IGF-I levels. Basal pretreatment levels of 123+/-18 microg/l were suppressed to 65+/-11 microg/l (mean suppression 47%, P < 0.001). These preliminary data confirm the inhibitory effect of tamoxifen on IGF-I production but seem to exclude the possibility that this effect may be due to an inhibition of GH secretion.

Plasma prolactin response to gonadotropin-releasing hormone during benzodiazepine treatment.

Previously we observed that prolactin (PRL) is secreted in response to gonadotropin-releasing hormone (GnRH) in normal women during the periovulatory phase of the menstrual cycle. Because sedative drugs affect the neurotransmitters involved in the regulation of PRL secretion, we investigated PRL responsiveness to GnRH in pre- and postmenopausal female subjects during prolonged treatment with benzodiazepines (six-60 months). In both pre-and postmenopausal patients who were not on benzodiazepine treatment, GnRH infusion (0.2 micrograms/min for 3 hr) was ineffective in eliciting a PRL response. In six premenopausal women treated with benzodiazepines, basal PRL concentrations were not influenced by the drug in four subjects (range 4.0-15.7 ng/ml) and were slightly elevated in two subjects (23 and 30 ng/ml). In six treated postmenopausal women, basal PRL concentrations were in the normal range (7.5-11.0 ng/ml). GnRH infusion induced a progressive increase in PRL concentrations which reached a peak at 120 min in the premenopausal subjects (mean % SEM increase: 64 +/- 30.5%) and at 60-90 min in the postmenopausal subjects (mean % increase: 110.6 +/- 34.7%). A saline infusion, performed on a separate day during benzodiazepine treatment as a control, did not influence PRL.

Calcium antagonists and hormone release. I. Effects of verapamil on insulin release in normal subjects and patients with islet-cell tumor.

Intravenous infusion of verapamil, an organic antagonist of calcium transport into cells, produced a marked and significant inhibition of glucose-, glucagon- and sulfonylurea-induced increases in serum insulin in normal subjects. Also, blood glucose concentrations remained significantly higher after the secretagogue plus verapamil than after the secretagogue alone. Blood glucose concentrations increased regularly after verapamil + glucagon administration indicating that verapamil is not capable of inhibiting the hepatic glycogenolysis induced by glucagon. Two patients with islet-cell tumor, treated with verapamil for 5 days, experienced a decrease in the severity and frequency of hypoglycemic attacks while "autonomous" insulin release was inhibited. The present results clearly show that calcium antagonists are capable of inhibiting insulin response to appropriate stimuli in normal subjects. Therapeutic association of calcium antagonists and sulfonylureas should be used with caution in the light of the present findings. Calcium antagonists can be useful drugs in the treatment of hypoglycemia caused by islet-cell tumor.

Evaluation of dopaminergic tone in hyperprolactinemia. III. Thyroid-stimulating hormone response to metoclopramide in differential diagnosis and postoperative follow-up of prolactinoma patients.

Recently, it has been shown that patients with a PRL-secreting pituitary adenoma have a greater thyroid stimulating hormone (TSH) release after dopamine (DA)-receptor blockade than normal subjects. We have compared the TSH and PRL responses to metoclopramide (MCP) in normal and postpartum lactating women with those in 28 patients with hyperprolactinemia of different origin. Patients with a PRL-secreting pituitary adenoma were also tested after transsphenoidal removal of the tumor in order to establish the prognostic value of this test in such patients. Following MCP administration, percent increases in plasma PRL levels were greater in normal female subjects than postpartum lactating women. Plasma TSH levels did not increase in postpartum women and had a modest increment in normal subjects. In patients with hypothalamic tumors and empty sella syndrome plasma PRL and TSH levels showed modest or no increases after MCP administration. In ten patients harboring a microprolactinoma, plasma TSH levels showed an exaggerated increment after DA-receptor blockade. Postoperatively, despite normal or borderline PRL levels in the immediate postoperative period, a TSH response to MCP was present (in five patients one to two weeks after the operation, and in five patients one to three years after the operation), suggesting an increased DA activity even in the absence of hyperprolactinemia. In conclusion, the TSH test can easily detect increased DA-activity in patients with a microprolactinoma both preoperatively and postoperatively. It is possible that some patients with increased DA-activity in presence of normal PRL levels and normal PRL responsiveness to stimulation will experience a recurrence of hyperprolactinemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Biphasic effect of estradiol on luteinizing hormone response to gonadotropin-releasing hormone in castrated men.

This study was designed to investigate the possibility that in men estradiol (E2) has a stimulatory effect on the gonadotropin response to GnRH. Nine castrated adult men, who presented extremely low testosterone (T) concentrations, received 5 mg/day estradiol benzoate (E2B) i.m. every 24 hr for several days, starting 5 days after orchidectomy. During E2B treatment the pituitary responsiveness to GnRH (100 micrograms given as an iv bolus) was tested after 24, 48, 72, 96, 120, and 144 hrs of E2B administration. The pituitary responsiveness to GnRH was also tested in untreated men from day 5 to day 10 following bilateral orchidectomy. In the E2B-treated subjects the increased serum estradiol concentrations induced an initial decrease and a subsequent increase of the LH response to GnRH. The responses were decreased after 24 hr of treatment; thereafter, the LH responses were progressively increased and were markedly augmented after 120 hr of E2B treatment. On the contrary, during treatment the FSH response to GnRH was preferentially blunted. In the untreated castrated men the LH and FSH responses to GnRH increased progressively from day 5 to day 10 after orchidectomy, but decreased responses were never observed during this period of observation. The maximum LH concentrations, which occurred at 30-60 min following GnRH in untreated castrated men, did not occur until 120-150 min in the E2B treated men.

Dopaminergic mechanisms regulating prolactin secretion in patients with prolactin-secreting pituitary adenoma. Long-term studies after selective transsphenoidal surgery.

Twenty-seven female patients with prolactin-secreting pituitary microadenoma, were studied at different intervals following selective transsphenoidal removal of the tumor. Postoperatively, all patients had normal prolactin (PRL) levels and regular menstrual cycles were restored. Sixteen of 27 patients showed positive responses to TRH and metoclopramide (MCP) within 1 mo after surgery. On the contrary, 9 patients showed evaluation of these patients demonstrated that normal neuroendocrine relationships were restored after several months since positive PRL responses to TRH and MCP could be elicited in such patients. The remaining 2 patients who showed basal PRL levels in the upper range of normal, exhibited negative responses to TRH and MCP. These patients had progressively to TRH and MCP exhibited 10-20 mo after surgery a normal decrease in PRL levels following administration of carbidopa plus L-Dopa. Negative responses to carbidopa plus L-Dopa were instead obtained in 6 postoperative patients with elevated PRL levels and negative responses to TRH and MCP. These results suggest that: 1) Hyperprolactinemia induced by "autonomous" pituitary adenomas increases hypothaLamic dopamine (DA) secretion, which in turn inhibits PRL secretion by nonadenomatous lactotropes. 2) Total selective removal of the microadenoma acutely decreases PRL concentration, but a functional inhibition of the normal lactotrope can persist for a period of few months following surgery in a certain number of patients. 3) Prolonged reduction of PRL concentration is accompanied to a normal DA tone with reestablishment of normal neuroendocrine relationships.

Estrogen dependence of the periovulatory plasma prolactin response to gonadotropin-releasing hormone in normal women.

It has been previously reported that GnRH is capable of inducing a PRL response in intact and castrated men treated with estradiol benzoate for 8-9 days. To further support the hypothesis of an estrogen-dependence of the PRL response to GnRH, GnRH was administered, either as a bolus or as a continuous infusion, to 45 normal women during various phases of their menstrual cycles. Synthetic GnRH (100 micrograms intravenous bolus) elicited a significant increase (mean 175%) in circulating PRL levels in nine women studied during the periovulatory phase of the menstrual cycle (days 14-17). Similarly, GnRH infusion (0.2 micrograms/min X 3 h) induced a PRL response (mean 148%) in six women studied during the same period. In contrast, saline infusion induced a modest decrease (37%) in plasma PRL levels in five women studied during the periovulatory period. No significant changes in circulating PRL levels were found after GnRH administration as a bolus or a continuous infusion, in 13 women during the late follicular phase (days 10-13) and in 12 women during the midluteal phase (days 21-24). Synthetic GnRH elicited the expected increase in gonadotropin levels during all phases of the cycle studied. The maximal response was found for both LH and FSH during the periovulatory phase of the cycle. In conclusion, the data confirm that GnRH is capable of stimulating a PRL response in humans and again suggest that this response is estrogen-dependent. Finally, a temporal correlation between the midcycle gonadotropin peak and the positive PRL response to exogenous GnRH has been established.