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A sequential stimulation by arginine infusion and LRF plus TRF injection for the release of five pituitary hormones (LH, FSH, GH, PRL, and TSH) as an integrated functional reserve test of the adenohypophysis was devised. The serial hormonal release elicited by sequential stimuli in normal male (N = 11) and normal female subjects (N = 11) was characterized; concomitant with a rise in GH, arginine induced a consistent increase in PRL levels; a simultaneous rise in serum TSH and PRL, and in LH and FSH occurred in response to TRF and LRF, respectively. The usefulness of this integrated reserve test was evaluated in patients with abnormal hypothalamic-pituitary axis; differentiation between hypothalamic vs. pituitary defect with single or multiple hormone involvement may be revealed in patients with hypopituitarism, amenorrhea-galactorrhea syndrome, and "hypothalamic amenorrhea." Thus, together with serum cortisol determinations, all trophic hormones of the adenohypophysis may be accurately assessed in this simple six-hour integrated test.

Of 28 patients presenting with amenorrhea-galactorrhea, pituitary tumors were confirmed in eight. Six patients had occult hypothyroidism and the rest had an endocrine profile suggestive of pituitary tumor or of an idiopathic etiology. Treatment with bromocryptine resulted in suppression of the inappropriate lactation and restoration of regular menstrual function. In five cases, however, the galactorrhea was only diminished and in four of these cases, normal ovarian function did not return. Of the 19 patients that were seeking fertility and continued the medication for at least 20 days, nine pregnancies resulted. A similar response to bromocryptine was observed regardless of the underlying cause of the amenorrhea-galactorrhea.28 women with amenorrhea-galactorrhea were investigated endocrinologically and treated with bromocryptine 2.5 mg twice daily, ranging from 18 to 150 days. These women were classified into 6 with hypothyroidism, having prolactin (PRL) over 30 ng/ml, thyroid stimulating hormone (TSH) over 8 mcU/ml, luteinizing hormone (LH)6-20 mlU/ml and greater than follicle stimulating hormone (FSH); 8 with radiologically diagnosed pituitary tumors, LH, FSH, and increased PRL; 9 with similar endocrine profiles and suspected pituitary tumors; and 3 with high PRL considered idiopathic. 5 of the hypothyroid group were followed, and achieved ovulation, reduced TSH, PRL, and lactation, and 3 became pregnant. Of the 8 with tumors, 5 menstruated, 4 ovulated, 3 conceived, 3 had reduced lactation, 2 had reduced PRL, and 1 failed to respond clinically; 9 with suspected tumors took bromocryptine for at least 20 days, resulting in 4 pregnancies and 3 with regular menses. The 3 idiopathic cases showed lower PRL and regular ovarian function, 1 pregnancy, yet 1 developed pseudocyesis and recurrent galactorrhea. 2 women had to stop bromocryptine because of vomiting. This drug is longer-acting than L-dopa and safer than estrogen-progestagen combinations in cases of pituitary tumors. Bromocryptine reduces galactorrhea and associated hypothyroidism temporarily.

Serum prolactin (PRL) levels in 16 premenopausal subjects on synthetic estrogen and progestin were measured during 19 treatment cycles. The studies were performed during the estrogen segments of the treatment cycle (days 7–16) in 10 subjects receiving sequential contraceptives, and between days 9–20 in 6 subjects receiving combination type contraceptives. Because of the episodic nature of PRL release, the transverse mean of the frequent samples obtained over a period of four hours was used for quantitative comparison of subjects receiving the contraceptive steroids with normal subjects. Significant increases in prolactin concentrations were noted in both sequential (P

Serum prolactin (PRL) concentrations and total estrogen levels were determined in groups of boys and girls from ages eight through 15. There was no significant change in PRL concentration with advancing age in boys, and levels were comparable to adult men. In girls, mean serum PRL and estrogen levels were not significantly different from ages eight through 13 and were comparable to those found in boys of the same age groups. At age 14 and 15, an increase in PRL and estrogen levels was found in girls.

Publisher Summary This chapter focuses on the investigations conducted over the past few years on the interaction between the hypothalamic hormone(s) and gonadal steroids in the regulation of cyclic gonadotropin output by the adenohypophysis in humans. It describes hypothalamus as a neuroendocrine regulator. It also reviews the observations on the biological actions of hypothalamic somatostatin in humans. The description of the hypothalamic-hypophysial portal system and the subsequent presentation of a number of anatomical and physiological observations led to the proposal that the hypothalamus is critically involved in the control of anterior pituitary function. The chapter presents the three elements of the hypothalamic-hypophysial portal system: (1) the CNS-hypothalamus complex that may be regarded as a signal generator, (2) the pituitary as a signal transmitter, and (3) the cyclic ovarian steroid output as a signal modulator. It reviews the regulation of the hypothalamic-hypophysial- gonadal system in humans within this general context.

The effects of large doses of estrogen on prolactin (PRL) release were assessed. Circulating PRL levels in response to intravenous infusion of 17 beta-estradiol (E2), at a rate of 50 mug per hour for 4 hours, were studied in 10 subjects, and a chronic administration of ethinyl estradiol (EE) at a dose of 400 mug per day, for 1 week, was evaluated in five hypogonadal subjects. There was a significant depression of serum level of PRL during the E2 infusion and a significant increase in PRL release after discontinuation of the infusion. The chronic treatment of large doses of EE induced a more rapid (within 36 hours) and a significantly greater elevation of PRL levels at the end of 1 week treatment than those found during smaller doses of EE administration, as reported previously. These data suggest that acute treatment of estrogen may have a biphasic action on the pituitary PRL section and that the augmentatory effect of estrogen on PRL secretion is dose-dependent in human beings.

A protein fraction with prolactin bioactivities was obtained from the culture medium of human fetal pituitary tissue in long term cultures and termed Pasteels human prolactin (PHP) for convenience. An antiserum was prepared against this human prolactin and used to develop a radioimmunoassay for the material in human plasma. The antigen available (220 µg) was tested against antisera to human growth hormone and to human placental lactogen and in radioimmunoassays for these hormones. The results suggested that the human prolactin fraction contained some immunoreactive human growth hormone (1%). The resulting antibodies in the antihuman prolactin serum could be neutralized by the addition of human growth hormone. The human prolactin also generated antibodies, binding 131I-labelled human prolactin, which were not neutralized by human growth hormone. This binding was inhibited by plasma from a normal male, 2 normal females and by plasma from a lactating woman after breast feeding. An increase in plasma concentration of the inhibitor, immunologically similar to the human prolactin fraction, was obtained after phenothiazine injection. In the 7 plasma samples tested for human prolactin only 1 contained a detectable concentration of immunoreactive growth hormone. Immunoreactive human placental lactogen (human chorionic somatomammotropin) or any material cross-reacting with anti-HCS serum was undetectable in these plasma samples by a sensitive radioimmunoassay. It is suggested that human plasmas contain detectable amounts of a material immunologically similar to a prolactin fraction isolated from tissue cultures of fetal pituitaries. The fraction and the plasma inhibitor are distinguishable by immunoassay from human growth hormone and from human placental lactogen. © 1971 S. Karger AG, Basel., SCOPUS: ar.j, info:eu-repo/semantics/published

Assessment of temporal relationship between levels of prolactin (PRL), gonadotropins, and ovarian steroids in 14 ovulatory cycles was made. Serum PRL concentrations were determined by a homologous radioimmunoassay. Our data showed that, although the highest mean PRL concentration was found on the day of LH-surge and the day after estrogen peak, a consistent pattern of circulating PRL in daily morning samples was not present in ovulatory cycles; variations in random fluctuation with erratic spikes were observed within cycles and between subjects. In two cycles studied, despite markedly elevated PRL levels (eightfold) induced by amphetamine, optimal ovulatory events occurred in terms of both hormonal patterns and luteal function. These findings implicate a lack of apparent physiologic role of PRL in the regulation of ovarian function in human subjects. The random daily fluctuation of PRL was further characterized in samples obtained at 10 to 30 minute intervals during different days of five ovulatory cycles and continuous sampling during day and night was made in three of five studies; a clear episodic nature of PRL release was disclosed. A circadian rhythm with marked elevation during sleep which was composed of multiple peaks with larger excursions than those found during waking periods was revealed. The event of sleep-induced PRL rise was initiated shortly (30 to 90 minutes) after the onset of sleep and ceased upon wakening. In one subject a quantitatively greater nocturnal PRL release around midcycle (eightfold) than during the follicular and the luteal phases (threefold) was found. These data would facilitate future elucidation of the inapparent role as well as the neuroendocrine regulation of PRL secretion during the human menstrual cycle.