Basal Serum PRL Levels Research Articles

Development of Anti-PRL (Prolactin) Autoantibodies by Homologous PRL in Rats: A Model for Macroprolactinemia

Macroprolactinemia is hyperprolactinemia in humans mainly due to anti-PRL (prolactin) autoantibodies and is a pitfall for the differential diagnosis of hyperprolactinemia. Despite its high prevalence, the pathogenesis remains unclear. In this study, we examined whether anti-PRL autoantibodies develop via immunization with homologous rat pituitary PRL in rats to elucidate what mechanisms are involved and whether they cause hyperprolactinemia with low PRL bioactivity, as seen in human macroprolactinemia. Anti-PRL antibodies were developed in 19 of 20 rats immunized with homologous rat pituitary PRL and 29 of 30 rats with heterogeneous bovine or porcine pituitary PRL but did not develop in 25 control rats. In rats with anti-PRL antibodies, the basal serum PRL levels were elevated, and a provocative test for PRL secretion using dopamine D2 receptor antagonist (metoclopramide) showed a normal rising response with a slower clearance of PRL because of the accumulation of macroprolactin in blood. Antibodies developed by porcine or rat pituitary PRL reduced the bioactivity of rat serum PRL, and gonadal functions in these rats were normal despite hyperprolactinemia. Anti-PRL antibodies were stable and persisted for at least 5 wk after the final injection of PRL. These findings suggest that pituitary PRL, even if homologous, has antigenicity, leading to the development of anti-PRL autoantibodies. We successfully produced an animal model of human macroprolactinemia, with which we can explain the mechanisms of its clinical characteristics, i.e. asymptomatic hyperprolactinemia.

Prolactinomas resistant to standard dopamine agonists respond to chronic cabergoline treatment.

Cabergoline (CAB), a new, potent, and long-lasting PRL-lowering agent, was shown to be effective in tumoral hyperprolactinemia. The aim of this study was to investigate the effectiveness of CAB in patients with prolactinoma proven to be resistant to bromocriptine (BRC) and quinagolide (CV 205-502). Twenty-seven patients (19 macro- and 8 microprolactinomas) were treated with CAB at a weekly dose of 0.5-3 mg for 3-22 months. All patients were previously shown to be resistant to BRC, and 20 of them were resistant to CV 205-502 as well. Basal serum PRL levels before CAB treatment ranged from 108-3500 micrograms/L in macroprolactinomas and from 64-205 micrograms/L in microprolactinomas. Gonadal failure was present in all patients, whereas symptoms of tumor expansion, such as visual field defects and headache, were present in 10 of 27 patients. Eight macroprolactinomas had previously undergone surgery and/or radiotherapy. CAB treatment normalized serum PRL levels in 15 of 19 macroprolactinomas and in all 8 microprolactinomas. In 3 of the remaining 4 patients it caused a notable decrease in prolactinemia (89%, 80.5%, and 68.7% of the baseline). Only 1 patient was withdrawn from CAB therapy after 3 months at the weekly dose of 2 mg due to the absence of any significant clinical, hormonal, or radiological improvement. Gonadal function was restored in 18 of 27 patients, galactorrhea disappeared in 5 of 6 women, and headache improved in 7 of 8 patients. A significant tumor shrinkage was detected by computed tomography and/or magnetic resonance imaging in 9 macroprolactinomas and 4 microprolactinomas. CAB was well tolerated by all patients, except 6 who referred slight and short-lasting nausea, postural hypotension, abdominal pain, dizziness, and sleepiness at the beginning of treatment. In particular, CAB was well tolerated by 19 patients previously shown to be poorly tolerant to BRC and CV 205-502. In conclusion, CAB may represent, at the moment, the only successful therapy for prolactinoma-bearing patients resistant to BRC and CV 205-502, as it normalized PRL levels in 22 of 27 patients, reduced tumor size in 13 of 27 patients, and improved clinical symptoms in 25 of 27 patients in the present study.

Thyrotropin and Prolactin Responses to Thyrotropin-Releasing Hormone in Premenstrual Syndrome*

Recent reports of altered TSH responsiveness to its releasing hormone (TRH) in women with premenstrual syndrome (PMS) suggested that subclinical hypothyroidism may be responsible for the mood changes, such as depression, that occur in these women. In this study we measured basal and TRH-stimulated serum TSH and PRL levels in 15 women with PMS and in 19 age-matched normal women. The mean baseline serum TSH concentrations were similar in the 2 groups in both the follicular [normal, 1.3 +/- 0.2 (+/- SE); PMS, 0.9 +/- 0.2 mU/L] and luteal (normal, 1.1 +/- 0.2; PMS, 1.1 +/- 0.2 mU/L) phases of the cycle. The mean baseline serum PRL levels also were similar in the 2 groups in the follicular (normal, 16 +/- 2; PMS, 13 +/- 2 micrograms/L) and luteal (normal, 13 +/- 2; PMS, 14 +/- 2 micrograms/L) phases of the cycle. After TRH administration, peak serum PRL and TSH levels were reached at 15 and 30 min, respectively, and the response curves were virtually identical in the 2 groups in both phases of the cycle. One normal woman had elevated basal and TRH-stimulated TSH concentrations compatible with subclinical hypothyroidism, but had normal noncyclic scores on her prospective rating scales. Our findings suggest that PMS is not associated with thyroid dysfunction or abnormal PRL secretion and that thyroid hormone replacement therapy is not indicated in this condition.

Effect of oral zinc administration on prolactin and thymulin circulating levels in patients with chronic renal failure.

High serum PRL and low zinc (Zn) levels are common findings in patients with chronic renal failure (CRF); in such patients serum Zn concentrations have been reported to be inversely correlated to serum PRL levels. Moreover, Zn regulates both thymus growth and the biological activity of the thymic hormone thymulin, and PRL-thymic interrelationships have been described. To determine whether hypozincemia alters serum PRL and plasma thymulin concentrations in CRF, 9 men with CRF treated by chronic hemodialysis were given 400 mg/day Zn sulfate, orally (4.96 meq/day Zn), for 6 months. Before treatment, serum PRL levels were significantly higher (P less than 0.001) in these patients than in normal men [mean, 28.7 +/- 20.7 (+/-SD) vs. 7.5 +/- 3.7 micrograms/L], and their serum PRL response to TRH (200 micrograms, iv) was impaired (mean maximal percent increase, 38.2 +/- 10.9 vs. 641 +/- 335; P less than 0.001). The plasma Zn-bound bioactive thymulin titer (1.3 +/- 0.7 1/log2), total thymulin titer (Zn-bound plus Zn-unbound forms, 2.1 +/- 0.8 1/log2), and serum Zn (13.1 +/- 2.4 mumol/L) were lower (P less than 0.001) in men with CRF than in normal men. Zn therapy did not induce any significant change in basal and TRH-stimulated serum PRL levels, while serum Zn levels significantly increased, reaching the normal range after the first week of treatment (17.8 +/- 6.3 mumol/L). Plasma total thymulin increased rapidly, reaching normal levels after 1 week, but Zn-bound thymulin increased modestly during the first month of treatment and more after 3 and 6 months of treatment. There was no age-related difference in plasma thymulin levels during therapy. We conclude that oral Zn administration in patients with CRF significantly increases both total and Zn-bound thymulin, but does not modify basal and TRH-stimulated serum PRL levels. The observation that Zn supplementation markedly increased plasma thymulin levels in uremic patients suggests that Zn is a potent stimulus for thymic hormone synthesis, and it can reverse the age-related diminution of thymic activity in CRF patients.

Zinc Does Not Acutely Suppress Prolactin in Normal or Hyperprolactinemic Women*

In rat pituitary cells in vitro physiological zinc concentrations selectively inhibit basal and stimulated PRL release. This study was done to investigate the serum PRL response to an oral zinc challenge in vivo. Eight hyperprolactinemic [mean serum PRL, 76.0 +/- 43.8 (+/- SD) micrograms/L] and 10 normal (mean serum PRL, 9.6 +/- 2.8 micrograms/L) women were studied. All women had normal thyroid, renal, and hepatic function, and none was taking any medications. Each was studied twice, after both oral zinc (50 mg) and placebo, given in random order. Blood was withdrawn every 15 min from 30 min before to 210 min after zinc or placebo administration; TRH (500 micrograms) was given iv at 180 min. Both hyperprolactinemic and normal women absorbed the zinc well, achieving similar maximal plasma zinc levels [hyperprolactinemic women, 39.5 +/- 6.9 (+/- SD) mumol/L; normal women, 33.3 +/- 7.0; P less than 0.001 vs. placebo]. When 2 women who became symptomatic after zinc administration were excluded, there were no significant differences in basal or TRH-stimulated serum PRL levels after zinc vs. placebo. These findings indicate that zinc is not involved in the acute in vivo regulation of PRL secretion in humans.

Inhibition of basal and metoclopramide-induced prolactin release by cabergoline, an extremely long-acting dopaminergic drug.

The aim of this study was to evaluate the effectiveness of the ergoline derivative cabergoline in inhibiting the serum PRL response to metoclopramide (MCP; 5 mg, iv) and the duration of this effect. Seven normal men received cabergoline (600 micrograms, orally) on day 0 and underwent a MCP test on days -1, 1, 4, 8, 15, and 28. Fasting serum PRL levels were significantly depressed from days 1-14; the nadir value occurred on day 4. MCP-induced PRL release was significantly inhibited up to day 28, with a nadir on day 4. Two months later, four of the men received placebo on day 0, and tests with MCP were performed on days -1, 8, and 28; basal serum PRL levels and PRL responses to MCP were superimposable on days -1, 8, and 28. These data indicate that cabergoline is an effective long-acting inhibitor of PRL release in normal men, suitable for use in the management of hyperprolactinemic patients.

Effects of sex and age on growth hormone response to growth hormone-releasing hormone in healthy individuals.

The influence of age and sex on human GH secretion is controversial. In previous studies, serum GH responses to arginine and insulin-induced hypoglycemia were significantly higher in pre- and postovulatory women than in men. In contrast, recent studies suggest that GH responsiveness to GHRH is higher in normal young men than in age-matched women. To clarify the question of sex and age influence on GHRH-(1-44)-stimulated GH secretion, we studied 116 normal women and men (with body mass indexes of 18-25 and 19-26, respectively) between the ages of 18 and 95 yr. The peak serum GH increments after GHRH administration were significantly higher in premenopausal women than in age-matched men (P less than 0.003 for the age group 18-30 yr and P less than 0.03 for the age group 30-50 yr, as assessed by analysis of variance). The responses were not different in postmenopausal women and age-matched men. Multiple regression analysis revealed a significant negative correlation between GHRH-induced GH responses (integrated area under the curve) and age in both women (P less than 0.002) and men (P less than 0.001). In addition, we determined basal serum testosterone, estradiol, cortisol, and PRL levels in all subjects. Multivariate regression analysis of the GH responses to GHRH administration revealed a significant positive correlation (P less than 0.01) between serum estradiol and both GH increase and the area under the GH response curve. No correlation was found between GHRH-stimulated GH secretion and basal serum cortisol, testosterone, or PRL concentrations. Our data clearly demonstrate a marked influence of both sex and age on GHRH-stimulated GH secretion. We found a higher GH increase in premenopausal women compared with age matched-men and an age-dependent decrease in GHRH-stimulated GH secretion in both sexes. Furthermore, in women a significant influence of estradiol on GH secretion after GHRH administration could be demonstrated.

Gradual recovery of lactotroph responsiveness to dynamic stimulation following surgical removal of prolactinomas: Long-term follow-up studies

Prolactin-secreting pituitary adenomas were selectively removed through a transsphenoidal approach from 120 women. Basal serum PRL levels (measured one to six months after surgery) were normal in 96 patients and decreased appreciably but not to normal in the remaining 24 patients. Dynamics of PRL secretion were studied at three to four months in 81 patients who had normal basal PRL level. Two different patterns of response to provocative stimuli were noted in these patients. In one group (group I, n = 65), patients had >100% rise in serum PRL following TRH or perphenazine (Pz) administration. However, when analyzed as a group, the mean ± SEM incremental responses (ΔPRL) to TRH and Pz in these patients (29.9 ± 1.9, 20.4 ± 1.5 ng/mL) were significantly less ( P < 0.005 and P < 0.001) than those of normal women (38.8 ± 5, 33 ± 5 ng/mL, respectively). Nineteen of these patients were restudied 12 to 72 months after surgery. The responses to provocative stimulation at that time were improved and similar to normal women. In contrast, in the second group (n = 16) of patients (group II), the responses to stimulation with the same agents were blunted or absent and remained so during subsequent studies. Recurrence of the hyperprolactinemia was noted in 11 of the 16 patients in group II and in only two of 65 patients in group I. The daily serum PRL levels in the immediate postoperative period were higher in patients from group II than those from group I. We conclude that transsphenoidal surgery is an optimal form of therapy for patients with PRL-secreting adenomas. The dynamics of PRL secretion are helpful in evaluating the outcome of surgery and in predicting patients at risk for recurrences. Following complete removal of the adenoma, lactotrophs of the normal pituitary recover gradually and their responsiveness to stimulation becomes normal months to years later. These findings are consistent with the concept that PRL-secreting pituitary adenomas are primary pituitary disorders.

Reversible hypopituitarism in patients with large nonfunctioning pituitary adenomas.

Detailed pituitary function studies were conducted on 26 patients with large nonfunctioning pituitary adenomas before and 2-3 months after transsphenoidal adenomectomy. Basal serum PRL, GH, TSH, LH, FSH, and ACTH levels were measured, and dynamic studies of their secretion were made. Preoperatively, GH deficiency was found in all 26 patients (100%), hypogonadism in 25 patients (96%), hypothyroidism in 21 patients (81%), and adrenal insufficiency in 16 patients (62%). Serum PRL levels were low (1.5-4 ng/ml) in 5 patients, normal (5-20 ng/ml) in 9 patients, and mildly elevated (21-53 ng/ml) in the remaining 12 patients. After selective adenomectomy, variable improvement in pituitary function occurred in 17 patients, worsening in 1 patient, and persistence of hypopituitarism in 8 patients. After surgery, normal thyroid function was documented in 12 of the 21 patients (57%) who were hypothyroid preoperatively. Similarly, 6 of the 16 patients (38%) with adrenal insufficiency recovered normal adrenal function, and 8 of the 25 patients (32%) with hypogonadism recovered normal gonadal function. GH deficiency persisted in all but 4 patients (15%). Serum PRL levels decreased in all patients, and only 5 had midly elevated levels after surgery. The presence of a normal or mildly elevated serum PRL level before surgery in these patients was of value in predicting possible recovery of pituitary function after surgery; none of the 5 patients with low preoperative serum PRL levels had any improvement in pituitary function after surgery. A rise in serum TSH levels after TRH administration before surgery also was helpful in predicting possible recovery from hypopituitarism. Most patients who had a rise in serum TSH level in response to TRH stimulation preoperatively recovered some pituitary function after adenomectomy. In contrast, no improvement in pituitary function occurred in patients who had blunted responses to TRH preoperatively. Improvement in pituitary function occurred more often in patients with tumors measuring 25 mm or less than in those with larger tumors. In conclusion, significant improvement in pituitary function may occur after surgical adenomectomy for nonsecreting pituitary tumors. A rise in serum TSH levels in response to TRH stimulation preoperatively suggested the presence of viable pituitary tissue in these patients with hypopituitarism. The presence of a normal or mildly elevated serum PRL level before surgery also suggested the presence of functioning pituitary lactotrophs. These observations suggest that compression of the portal circulation is a possible mechanism for hypopituitarism in this setting.(ABSTRACT TRUNCATED AT 400 WORDS)

Modulation of the prolactin response to thyrotropin releasing hormone by ovarian steroids in ovariectomized turkeys ( Meleagris gallopavo)

The effect of thyrotropin releasing hormone (TRH) administered intramuscularly (im) on serum levels of prolactin (Prl) in ovariectomized (ovx) adult turkeys before and following the onset of photostimulation, before and during daily administration (im) of progesterone (P; 0.1, 0.4, or 1.0 mg/kg), estradiol benzoate (EB; 0.01, 0.1, or 0.2 mg/kg), or their combination (1.0 mg/kg EB + 0.1 mg/kg P) were studied. Ovariectomy reduced Prl levels in the serum of photostimulated turkeys, and blunted the Prl response to TRH administration. Progesterone treatment had no effect on basal serum Prl levels but the Prl response to TRH was higher in P-treated turkeys than in non-treated ovx turkeys. Basal serum Prl levels were higher ( P < 0.05) in the EB-treated ovx turkeys than in the untreated birds. The Prl response to TRH in ovx EB-treated turkeys was greatly increased ( P < 0.05). Progesterone treatment of EB-primed ovx turkey did not alter the basal levels of serum Prl or the Prl response to TRH administration. These results suggest that ovarian steroids may be responsible for the increased Prl secretion in the female turkey associated with laying.

Prolactin secretion in acromegalic patients before and after selective adenomectomy.

PRL secretion before and after transsphenoidal adenomectomy was studied in 13 patients with acromegaly. Six patient had elevated basal serum PRL levels before surgery, while 7 patients had normal levels. In every patient, the basal serum GH level decreased to less than 5.0 ng/ml after surgery. In the group (group A) with high basal serum PRL levels (mean +/- SD, 41.3 +/- 5.8 ng/ml) before surgery, the PRL levels decreased significantly (P less than 0.0002) to less than 10.0 ng/ml (4.8 +/- 3.6 ng/ml) after the operation. However, in the group (group B) with normal levels (10.8 +/- 4.4 ng/ml) before surgery, PRL levels changed little (7.8 +/- 3.1 ng/ml) after the operation. In group A, the increment of PRL after TRH injection decreased or disappeared (P less than 0.02; 4.1 +/- 2.4 ng/ml) after surgery compared with that before surgery (39.2 +/- 25.9 ng/ml). On the other hand, in group B, the increment of PRL after TRH injection was nearly unchanged (17.1 +/- 7.0 ng/ml) after surgery compared with that before surgery (19.3 +/- 8.0 ng/ml). The results indicate that PRL is secreted from the pituitary adenoma in acromegalic patients with hyperprolactinemia, while PRL secretion from the normal part of the pituitary gland is decreased.

In vivo effects of progestins on prolactin secretion.

To assess a possible inhibitory effect of progestins on PRL secretion, serum PRL and estradiol levels were determined in 13 women with hyperprolactinemia due to a pituitary microadenoma before and after 3 months of treatment with a potent progestin, lynestrenol. PRL levels also were assessed during a TRH challenge test before and after treatment. Results were compared to those obtained in 10 normal women studied during the early follicular phase of their menstrual cycle and at the end of 3 months of treatment. The PRL response to TRH was blunted in patients before lynestrenol therapy. After therapy, basal serum PRL levels were significantly decreased, and the response to TRH was almost abolished. No change occurred in the normal women. The estradiol level was 80.5 +/- 7.5 (+/- SEM) pg/ml in patients before treatment and decreased to 29.2 +/- 5.0 pg/ml after therapy. Therefore, lynestrenol, a potent 19-nortestosterone derivative, exhibits in vivo an anti-PRL effect that could be related to its antiestrogenic and/or androgenic activities.

Endocrine Comparison of Obese Menstruating and Amenorrheic Women

10 examine the relationship between obesity and chronic anovulation, we compared basal serum LH, FSH, and PRL levels, determined at 20-min intervals, and basal C21 [progesterone, 17- hydroxyprogesterone , pregnenolone, 17-hydroxypregnenolone ( 17Pe ), and cortisol], C19 [testosterone (T), delta 4-androstenedione (A), and dehydroepiandrosterone] and C18 (estrone and estradiol) steroid hormone concentrations measured at 1- to 2-h intervals for a 24-h period in five normal weight cycling women (NC) and in two groups of weight-matched obese women. Five of the obese women were regularly cycling (OC), and six were amenorrheic (OA). Sex hormone-binding globulin (SHBG) and non-SHBG-bound T and estradiol concentrations were also measured in each woman. Compared to NC women, OC women had normal basal protein and steroid hormone concentrations, except for reduced 17Pe levels (P less than 0.05). Mean SHBG concentrations were reduced by approximately 30%, and non-SHBG-bound T was increased by 70%, although the differences were not significant. In addition, when six precursors of testosterone (pregnenolone, 17Pe , dehydroepiandrosterone, progesterone, 17-hydroxyprogesterone, and A) were considered together as a group and the data analyzed by the kappa 2 test, a reduction in basal levels of these precursors was found in OC women relative to those in NC women (P less than 0.005). In OA women, mean concentrations of SHBG were markedly reduced and those of total T, A, estrone, and non-SHBG-bound T were significantly increased compared to those in both NC and OC women. Mean 24-h concentrations of LH tended to be greatest and FSH lowest in this group, but were not significantly different from those in the other groups. The mean LH pulse frequency was significantly greater in OA than in OC women (P less than 0.05). Mean 24-h PRL and cortisol levels were also reduced in OA women relative to those in NC women. These data suggest the possibility of a compensatory decline in total T production in OC women in an attempt to maintain normal hormonal homeostasis; as a consequence, ovulation continues in a cyclic fashion. In OA women, such compensatory mechanisms are no longer operative. Instead, a central and/or peripheral defect, resulting in overproduction of androgen, may also exist and lead to anovulation in OA women. In conclusion, our data imply that obesity is not a primary factor causing chronic anovulation. However, obesity may aggravate an already existing subtle defect in some women and result in amenorrhea.

Hypothalamic-pituitary-testicular function in men with PRL-secreting tumors.

We studied the hypothalamic-pituitary-gonadal system in 33 men with PRL-secreting tumors to determine at which level(s) high PRL levels interfere with testicular function. In basal conditions serum PRL levels ranged between 24-4500 ng/ml, serum LH and FSH concentrations were lower than normal in 61% and 39% of patients; low testosterone (T) levels and sexual impotence appeared more common (85% and 88%) than that we expected on the basis of gonadotropin deficiency. Mean T increase after hCG in 14 patients with prolactinomas was significantly less than in normals (3.3 +/- 0.7) ng/Ml vs 7.3 +/- 0.5 ng/ml; p less than 0.025); a significantly higher T response to hCG was obtained in 5 cases retested after PRL levels had been reduced by therapy. GnRH test induced a normal LH rise in 45% of patients, Mean serum LH increase after clomiphene administration did not differ from that in normals, though 4 out of 10 patients showed an impared response. Metoclopramide injection did not cause a rise of LH in 11 patients so tested. These data, while not excluding a central influence of PRL on LHRH, suggest that in men the antigonadotropic effects of PRL are mainly exerted at the gonadal levels.

Serum prolactin after chest wall surgery: elevated levels after mastectomy.

Galactorrhea is a recognized sequel of chest injury, but serum PRL levels in these patients have not been systematically documented. Therefore, we examined the PRL responses over 5 days in patients undergoing either mastectomy (10 patients) or thoracotomy (10) and in seven patients undergoing elective laparotomy (controls). Basal serum PRL levels were normal in every subject. There were no consistent or significant alterations in PRL levels after laparotomy or thoracotomy. After mastectomy, PRL levels rose from a mean preoperative level of 7.1 +/- 1.3 to 16.0 +/- 3.3 ng/ml (P < 0.01) on the first postoperative day. Mean levels continued to rise to 35.6 +/- 6.6 ng/ml (P < 0.005) on day 5; levels were supranormal in eight subjects. Hyperprolactinemia persisted in the four subjects evaluated 4 weeks postoperatively and in one of five patients evaluated at 6 months. In a retrospective study, serum PRL levels were measured months to years after thoracotomy (31 patients) and mastectomy (53 patients) and compared to levels in 41 normal female controls. Mean serum PRL levels were 8.4 +/- 1.3 ng/ml in the control group, 13.1 +/- 0.9 ng/ml in the thoracotomy group (P < 0.005), and 20.6 +/- 3.1 ng/ml in the mastectomy group (P < 0.001). One thoracotomy patient and 18 mastectomy patients (34%) had supranormal PRL levels. It is concluded that mastectomy acutely stimulates PRL secretion in most subjects, and levels may remain elevated for months, perhaps for years, in a proportion of patients. Both the acute and chronic hyperprolactinemic states are probably the result of neurogenic PRL release mediated via the suckling reflex.

Prolactin-secreting pituitary microadenomas. II. Evaluation of surgical treatment

The authors evaluated results of surgical treatment for 12 cases of prolactin-secreting pituitary microadenomas with respect to the effect on the endocrinological status and compared these results with those for 10 cases of macroadenomas. The cases of microadenomas were all female; 10 cases with amenorrhea and galactorrhea, a case with oligomenorrhea and galactorrhea and a case with only amenorrhea. Both microadenomas and macroadenomas were operated on through the transsphenoidal route. Microadenomas were considered to have been removed completely but macroadenomas were not always removed completely because of their larger size. The relation between operative findings of microadenomas and basal serum PRL levels was analysed. Two elastic and firm adenomas showed elevated serum PRL levels (p<0.001) exceeding 400 ng/ml and two eosinophilic and two mixed adenomas showed higher serum PRL levels than the chromophobes (p<0.01). Adenomas with serum PRL levels around or over 200 ng/ml were all peripheral types. Localization within the sella turcica or size of the tumors had little relation to serum PRL levels. In microadenomas, serum PRL levels fell to the normal level in nine cases (75.0%) within a month after the operation. Three cases with normal PRL levels, however, gradually returned to elevated levels in the follow-up after a month. Conversely, no drop to the normal level was observed in cases of macroadenomas. Surgical impacts on HGH, TSH, LH, FSH and ACTH reserves were examined. Only four out of 18 cases (22.2%) among the microadenomas and macroadenomas had impaired hormonal reserves after transsphenoidal surgery which was considered to be a safe procedure. Regular menses were restored in nine out of 12 cases (75.0%) of microadenomas after a mean interval of a month and a half after the operation. Six cases showed ovulatory menses. One case experienced normal delivery and two cases became pregnant among the six patients. Galactorrhea disappeared in nine out of 11 cases (81.8%) of microadenomas after a mean interval of 2 months and a half after the operation and another case showed a remarkable decrease in lactation. However, none of the seven cases of macroadenomas showed restored menses, only one out of six cases had cessation of lactation and another two cases showed a decrease in lactation after the operation. Transsphenoidal removal of prolactin-secreting microadenomas was a safe and satisfactory treatment of choice.

Serum LH increase after estradiol and progesterone administration in hyperprolactinemic women

Intramuscular administration of 1.0 mg estradiol benzoate (E2B) did not cause serum LH to rise in 8 out of 9 hyperprolactinemic women (serum PRL: 39–187 ng/ml, mean: 93 ± 16.4 ng/ml SE). In these patients gonadotropin releasing hormone (GnRH) injection elicited normal or exaggerated gonadotropin responses. A significant increase in serum LH concentration (35±6.5 mlU/ml, p<0.001 vs. basal values) was observed in six of these patients when 25 mg progesterone (P) were given 36 h after E2 B. LH peak occurred 12 h (3 patients) and 36 h (the other 3 patients) after P administration. Twelve hours after P injection, a marked increase in serum FSH concentration was also noted in 2 patients. In the only patient responsive to both tests E2B + P administration induced a LH peak 24 h earlier than E2B alone. No correlation was found between LH behavior and basal serum PRL levels, and between the magnitude of LH response to E2B + P and to GnRH (25 μg iv). These data suggest that the reduced P production by the ovary may be one of the mechanisms by which hyperprolactinemia induces amenorrhea and anovulation; furthermore, they suggest that the occurrence of a LH peak after E2B + P administration might be due either to a real P dependent positive feedback mechanism, or to a recovery of a normal sensitivity of the hypothalamic peptidergic neurons to estrogens.

Response of human growth hormone, prolactin and thyrotropin to thyrotropin releasing hormone in liver cirrhosis and diabetes mellitus.

Serum HGH, PRL and TSH responses to intravenous injection of 500μg of TRH were investigated in nine patients with liver cirrhosis and in patients of the same number with diabetes mellitus who served as controls. They were roughly matched in age, sex and body weight. The basal serum HGH levels in the cirrhotic group were significantly high with a value of 4.7±1.7ng/ml compared to the values of 1.5±0.9ng/ml in the control diabetic group. Serum HGH levels in the cirrhotic group at 15, 30, 60 and 90min intervals after TRH were significantly higher than the basal serum HGH levels. The control diabetic group showed no positive response. Similar responses were observed again in three subjects of the cirrhotic group after treatment for hepatic insufficiency. Two subjects of the cirrhotic group showed an elevation of serum HGH in response to TRH even under hyperglycemia induced by glucose administration. The basal serum PRL levels were identical in both groups. The serum PRL levels in both groups evidently increased in response to TRH with significantly higher response in the cirrhotic group than in the control diabetic group at15, 30 and 60min intervals after TRH. There was no significant difference in the basal levels of serum TSH or the levels after TRH between both groups. It was concluded that the serum HGH levels in cirrhotic patients were elevated by TRH. Since the response was independent of clinical severity, the possibility exists that it could be attributed to some basic metabolic abnormality of the underlying liver cirrhosis. Since the abnormal HGH response to TRH was not seen in the control diabetic group and was not altered by hyperglycemia in the cirrhotic group, an abnormality of the glucose metabolism was eliminated as a possible cause.

Changes in luteinizing hormone and prolactin control mechanisms produced by glutamate lesions of the arcuate nucleus.

Lesions of the arcuate nucleus and retina were produced by ip administration of 4 g/kg monosodium glutamate to rats on days 2,4, 6, and 10 after birth, and all experimental work was continued at about 3–5 months of age. In agreement with earlier studies, we noted a striking reduction in the number of cell bodies in the arcuate nucleus, a marked degeneration of the visual system, and smaller anterior pituitaries, ovaries, uteri, testes, and seminal vesicles in adult rats that had been treated with glutamate during the neonatal period. A 60% reduction in the concentration of dopamine in the medial-basal hypothalamus and irregular estrous cycles also were observed in glutamate-treated groups. In two of six groups of glutamate-treated rats, basal serum LH levels were lower than in controls, whereas in one of six groups, PRL was elevated. The remainder of glutamate-treated groups showed no significant change in basal serum PRL or LH levels. After ovariectomy, serum LH levels were lower in glutamate-treated rat...

Serum prolactin and hypothalamic dopamine in rat strains selectively bred for differences in susceptibility to stress.

Rat strains selectively bred for behavioral differences in susceptibility to mild stress exhibited differences in serum prolactin (Prl) and hypothalamic dopamine (DA). Male rats from the Maudsley Reactive (MR) strain had higher levels of serum Prl and hypothalamic DA than rats from the Maudsley Non-Reactive (MNRA) strain. MR rats also showed a greater percentage increase in serum Prl 1 h after blockade of catecholamine synthesis by administration of alpha-methylparatyrosine (alphaMpT). The correlation of basal serum Prl levels with individual susceptibility to stress constitutes further evidence that Prl may play a functional role in the organism's response to stress. Strain differences in hypothalamic DA function may play a role in the etiology of strain differences in serum Prl.