Kuew-Hsiung Lu

Serum Prolactin Levels in Rats with Pituitary Transplants or Hypothalamic Lesions

Serum prolactin levels were determined by radioimmunoassay in hypophysectomized, ovariectomized rats bearing 0, 1, 2, or 4 anterior pituitaries (AP) underneath the kidney capsule at 1, 2, 4, 6, 8, and 10 weeks after transplantation. Rats with no AP transplants had barely detectable levels of serum prolactin, whereas rats with 1 AP transplant from female cycling rats had serum prolactin values as high as those seen in estrous rats (120 ng/ml serum). In rats bearing 2 AP transplants, serum prolactin increased to 170 ng/ml serum, whereas 4 AP transplants elevated serum prolactin to 250 ng/ml, which is about equivalent to that in lactating postpartum rats (280 ng/ml). Injections of estradiol benzoate (1 µg/day for 5 days) into rats bearing 0, 1, 2, or 4 AP transplants, beginning 10 weeks after transplantation, increased serum prolactin over pre-treatment levels, except in the rats with no pituitary transplants. Bilateral lesions placed in the median eminence or anterior hypothalamus of ovariectomized rats significantly increased serum prolactin to 125 and 85 ng/ml, respectively, as compared with sham-lesioned controls (20 ng/ml). Posterior hypothalamic lesions increased serum prolactin concentration slightly and lesions in the amygdaloid nuclei had no effect. These results indicate that removal of hypothalamic inhibition of prolactin release by pituitary transplantation or by appropriate lesion placement in the hypothalamus results in elevated serum prolactin levels.

Inhibition by L-Dopa and Monoamine Oxidase Inhibitors of Pituitary Prolactin Release; Stimulation by Methyldopa and d-Amphetamine

Summary A single intraperitoneal injection of L-dopa, the precursor of dopamine, into female rats significantly reduced serum prolactin concentration at 30 min, 1 hr, and 2 hr after injection compared to pretreatment levels or control rats not given this drug. A single injection of each of 3 monoamine oxidase inhibitors, pargyline, iproniazid or Lilly-15641, also significantly decreased serum prolactin below pretreatment values. Injection of L-dopa and pargyline together was more effective than either alone in lowering serum prolactin. Each of the above drugs is believed to reduce pituitary prolactin release because it increases catecholamine activity in the hypothalamus. By contrast, a single injection of methyldopa, which inhibits catecholamine synthesis, increased serum prolactin many fold over pretreatment levels. A single injection of d-amphetamine, a sympatheticomimetic drug, also greatly increased serum prolactin concentration. Addendum The hypothalami of the rats treated with saline (controls), iproniazid, pargyline, L-dopa or pargyline and L-dopa together, were assayed for PIF activity by our standard in vitro procedure. All drugs increased hypothalamic PIF activity and the combination of pargyline and L-dopa was more effective than either alone. These observations suggest that the increase in hypothalamic catecholamines produced by these drugs results in increased hypothalamic PIF activity, and this in turn depresses prolactin release by the pituitary.

Positive feedback by estrogen and progesterone on LH release in old and young rats.

Summary Young cycling rats 60 to 70 days of age, and old irregular-cycling or con-stant-estrous rats 10 to 11 months of age were ovariectomized. At 25 or 52 days after ovariectomy, they were each given a single injection of 8 μg of estradiol benzoate/100 g of body weight, followed 72 hr later by a single injection of 0.8 mg of progesterone/ 100 g of body weight. Radioimmunoassay of serum LH from blood samples removed 4,6,8, and 10 hr after progesterone administration showed that LH rose significantly more in the young than in the old, former constant-estrous rats 25 days after ovariec-tomy, and more than in either group of old rats at 55 days after ovariectomy. These results indicate that the positive feedback of estrogen and progesterone on LH release is reduced in old as compared to young cycling female rats, and is believed to account at least in part for the irregular cycling, and failure of ovulation in the old constant-estrous rats.

Effects of hypo- and hyperthyroidism on 5-hydroxytriptophan and chlorpromazine- induced prolactin release in the rat.

Pituitary prolactin (PRL) content was reported to be decreased in hypothyroid animals (1, 2). Serum levels of PRL as measured by radioimmunoassay were observed to be unchanged by hypothyroidism in rats and human subjects (3, 4). Recently, the response of PRL secretion to thyrotrophin-releasing hormone (TRH) was shown to be higher in hypothyroid than in euthyroid animals, and the stimulating action of TRH on prolactin release was abolished by treatment with thyroid hormones (4, 5). Onishi et al. (6) reported that PRL release in response to TRH and to chlorpromazine (CPZ) was eliminated in hyperthyroid humans. The precursor of 5-hydroxytryptamine (5-HT), 5-hydroxytryptophan (5-HTP), and CPZ, an adrenergic receptor blocker, both have been observed to greatly increase PRL secretion (7-9), perhaps by decreasing prolactin release-inhibiting factor (PIF) or by increasing prolactin releasing factor (PRF) in the hypothalamus (9). Materials and methods. Mature male Sprague-Dawley rats weighing 200-225 g were obtained from Spartan Research Animals (Haslett, Mich.). The rats were housed in a light-(14 hr light and 10 hr darkness daily) and temperature-controlled (26 ± 1°) room, and Received Wayne Lab Blox rat pellets (Allied Mills, Chicago, Ill.) and tap water ad libitum. The rats were grouped as follows: (1) intact controls, (2) thyro-parathyroidectomized (THX), (3) THX and 2.5 μg thyroxine (T4) per 100 g body wt, (4) THX and 10 pg T4 per 100 b body wt. All surgically treated rats were given 0.2 ml Longicil (Fort Dodge Laboratories, Inc., Fort Dodge, Iowa), an antibiotic, by im injection to avoid infection. The sodium salt of L-T4 (Nutritional Biochemical Co .) was dissolved in slightly alkaline saline (pH 8.0) and given sc to groups of three and four rats once daily. Rats in the intact control and THX groups were injected with alkaline saline (pH 8.0) only. After operation, the THX rats were given 1% calcium lactate solution instead of tap water to prevent tetany.