Marappa G. Subramanian

Association of sperm receptor activity with a purified pig zona antigen (PPZA)

Three types of data are presented which suggest that sperm receptor activity is associated with a 58,000 Mr acidic glycoprotein (PPZA) isolated from pig zonae: (1) boar sperm fail to bind to pig zonae pretreated with univalent antibody to PPZA; (2) boar sperm pretreated with PPZA are inhibited in binding to intact pig zonae; (3) binding studies utilizing boar sperm and radiolabeled PPZA indicate an inhibition of radiolabeled PPZA binding to sperm by non-labeled PPZA in a dose-related manner. Collectively these data suggest that, at least in the pig system, the contraceptive action of zona antibodies is accomplished by a specific immunologic reaction between antibody and the zona sperm receptor site rather than to a non-specific blockage of this receptor.

Effect of varying dosages and adjuvants on antibody response in squirrel monkeys (Saimiri sciureus) immunized with the porcine zona pellucida Mr = 55,000 glycoprotein (ZP3).

ABSTRACT: Using the porcine zona pellucida Mr = 55,000 (ZP3) glycoprotein as immunogen, the effect of varying ZP3 dosages (50 μg, 25 μg, 5 μg) or adjuvants (200 μg ZP3 with either Freunds, Al[OH]3, or a muramyl dipeptide analog [MDP] on antibody response was evaluated in female squirrel monkeys. Although the dosage range investigated did result in dose‐dependent titration profiles, antisera from all dosage groups demonstrated in vitro contraceptive potential. MDP was as effective an adjuvant as Freunds in eliciting high titers of antibodies demonstrating contraceptive potential. Al(OH)3 was not an effective adjuvant in this system. Fertility data, utilizing those monkeys in the dosage study, suggested that an RIA titer >40% binding was necessary to prevent pregnancy. We conclude that in the squirrel monkey system, a 50 μg dosage of ZP3 should be adequate for inhibiting fertility and that MDP would serve as a satisfactory alternative adjuvant for Freunds.

Alcohol inhibits suckling-induced prolactin release and milk yield

The effects of acute administration of alcohol on suckling-induced prolactin (PRL) release and milk yield were studied in primiparous lactating rats. On lactation day 2, pups were culled to 8 per litter. On day 5, dams were implanted with atrial catheters. On day 10, pups were separated from the dams at 0900 hr; at 1300 hr, an extension containing heparin (50 IU/ml) and 0.9% saline was attached to the exteriorized portion of the catheter. At 1400 hr, 0.4 ml blood was removed and replaced with 0.9% saline (control) or 0.3, 0.5 or 1.0 g/kg body weight of alcohol. At 1500 hr a second blood sample was obtained followed by a second alcohol or saline infusion. Pups were returned to dams and blood samples were obtained 10, 30, and 60 min after suckling. Milk consumption was calculated by weighing pups before and after 60 min of suckling. PRL in plasma samples was measured by radioimmunoassay. Alcohol did not alter baseline serum PRL. However, suckling-induced PRL release and milk consumption by the pups were significantly inhibited. Since basal PRL was not altered following administration of alcohol, the inhibitory effect of alcohol on suckling-induced PRL release is attributed to a disruption of transmission of the impulse arising from suckling stimulus.

Alcohol Inhibits Suckling-Induced Oxytocin Release in the Lactating Rat

Oxytocin release in response to suckling was examined in primiparous lactating rats following alcohol administration. Lactating rats, with litters adjusted to eight pups on day 2, were implanted with an atrial catheter between days 6 to 8 of lactation. Four days later, alcohol in doses 0.0, 1.0, or 2.0 g/kg BW was infused, and blood alcohol levels achieved following infusion of initial doses were maintained for 4 h. On the day of alcohol infusion, pups were separated from the dams at 8:00 A.M. Following completion of alcohol infusion, a baseline blood sample was obtained, pups were returned to the dams, and additional samples were obtained 5, 10, 30, and 60 min after suckling started. Oxytocin levels in plasma were determined by radioimmunoassay. Suckling latencies and milk consumption during the 60 min of suckling were determined. Alcohol administration inhibited suckling-induced oxytocin release across all time points. Suckling latencies among groups were comparable. Milk consumption by pups during the 60 min of suckling was lower for the alcohol administered groups. The data from the present study demonstrate that acute alcohol administration to lactating rats inhibits suckling-induced oxytocin release resulting in reduction of milk secretion.

Olfactory bulbectomy prevents the gonadal regression associated with short photoperiod in male golden hamsters

In male rats, pre-pubertal olfactory bulbectomy (BX) unmasks photoperiodic responsiveness so that maintenance of BX animals on short photoperiod results in a pineal gland mediated gonadal regression (Nelson and Zucker, Neuroendocrinology, 32 (1981) 266). The objective of the present study was to determine the effect of BX in Syrian hamsters, a species where short photoperiod alone induces a pineal gland induced testicular regression. Pre-pubertal (25-days old) Syrian hamsters underwent either sham BX, BX, or pinealectomy (PX) plus BX. One half of each group was then placed on an LD 14:10 photoperiod and the other half on LD 6:18. Thirteen weeks later all animals were decapitated. In the animals on LD 14:10, BX resulted in a slight but highly significant increase in testes weight but had no effect on other parameters examined. Sham BX hamsters on LD 6:18 had regressed testes and reduced serum testosterone levels, but these effects of short photoperiod were reversed in BX hamsters, so that the testes and seminal vesicles remained large. In addition, serum LH and testosterone levels were elevated following BX of the animals on LD 6:18. These results indicate that the olfactory bulbs tonically inhibit the reproductive system even in male hamsters maintained on long photoperiod and that olfactory bulbectomy prevents gonadal regression in male Syrian hamsters on short photoperiod, an effect which is the opposite of results obtained in rats on short photoperiod. Elucidation of the neural pathways involved and the nature of the relationship between the olfactory bulb and the pineal gland or photoperiodism remains for further investigation.

Effects of symptomatic status and the menstrual cycle on hot flash-related thermoregulatory parameters.

Objective: To compare core body temperature variation, sweating thresholds, and sweat rate in symptomatic and asymptomatic postmenopausal women and in eumenorrheic women in the follicular and luteal phases. Design: Twelve symptomatic and 10 asymptomatic postmenopausal women and 12 eumenorrheic women were recorded in a temperature- and humidity-controlled laboratory during thermoneutral and warm conditions. Core body temperature variation was measured with an ingested radiotelemetry pill, basal body temperature with a rectal thermistor, skin temperature with four skin surface thermistors, and sweat rate with a capacitance hygrometer. Results: Symptomatic women had significantly lower sweating thresholds and higher maximum sweat rates compared with all other women. These results could not be explained by differences in estrogen, progesterone, or body mass index. Conclusions: Postmenopausal women with hot flashes are uniquely characterized by low sweating thresholds and high sweat rates, relative to asymptomatic and eumenorrheic women.

Ectopic prolactin secretion from a gonadoblastoma

A 6.5‐year‐old girl developed isosexual, pseudoprecocious puberty secondary to a gonadoblastoma. The tumor was found to produce and secrete both immunoassayable and boiassayable prolactin based on immunohistochemical techniques and the presence of a prolactin gradient between the tumor vein and peripheral vein. The source of the prolactin was a Sertoli‐like cell. Neither growth hormone nor growth hormone‐releasing hormone was detected within the tumor. This case confirms the ectopic production of prolactin by neoplastic tissue.

Comparative effects of prenatal cocaine, alcohol, and undernutrition on maternal/fetal toxicity and fetal body composition in the Sprague-Dawley rat with observations on strain-dependent differences.

Pregnant rats received either 20, 30, 40, or 50 mg/kg cocaine HCl (SC) twice daily from gestation days 7 through 19. Pair-fed and untreated control groups and a group receiving 3.0 g/kg alcohol (PO) twice daily served as comparison groups. Females were sacrificed on gestation day 20 and the fetuses examined. Maternal weight gain and food consumption showed dose-dependent decreases. Maternal water consumption, by contrast, was significantly increased in the cocaine-treated animals and may reflect a diuretic effect. The maternal mortality rates in Sprague-Dawley rats were less than in two strains of Long-Evans rats, suggesting important strain-dependent differences in susceptibility to cocaine toxicity. Cocaine caused a significant dose-dependent decrease in fetal weights. Physical anomalies in the cocaine-exposed and alcohol-exposed fetuses included occasional hemorrhaging, edema, anophthalmia, and limb reduction. Despite increased maternal water consumption by cocaine-treated dams, there were no increases in fetal body water content. There were, however, significant decreases in fetal body fat content in the pair-fed, alcohol-treated, and two highest cocaine-treated groups.

The Olfactory Bulbs Tonically Inhibit Serum Gonadotropin and Prolactin Levels in Male Hamsters on Long or Short Photoperiod

Bilateral removal of the olfactory bulbs (BX) inhibits the testicular regression associated with maintenance of golden hamsters on short photoperiod (10L:14D). The present study was done to examine the reproductive endocrine changes following BX of hamsters, to test whether BX increases gonadotropin secretion by enhancing the rate of metabolism of peripheral testosterone, and to determine whether BX inhibits the response to photoperiod by blocking chemosensory signals from conspecifics.

Influence of Cholinergic Receptor Blockade on Drug-Induced Prolactin Release in the Monkey

The influence of varying doses of perphenazine, thyrotropin-releasing hormone (TRH) and serotonin on prolactin release was examined in two species of monkeys: rhesus (Macaca mulatta) and crab-eating (Macaca fascicularis). The intravenous administration of 0.33 mg/kg body weight of perphenazine or 1.0 mug/kg body weight of TRH gave a greater release of prolactin than higher doses of perphenazine (1.0 mg/kg) or TRH) (3.4 mug/kg), respectively. Prolactin release induced by serotonin at doses of 1, 5 and 10 mug/kg was similar. Both atropine sulfate (Atr-SO4) and atropine methyl nitrate (Atr-MN) at a similar base level potentiated the prolactin releasing action of the high dose of perphenazine suggesting that high doses of perphenazine activate a cholinergic inhibitory component present in the pituitary. Atropine sulfate had no potentiating action on the TRH-induced prolactin release, while Atr-MN appeared to prolong the response of TRH without potentiating it. Neither form of atropine had any influence on serotonin-induced prolactin release. The data indicated that the lower prolactin response to high doses of perphenazine and TRH were brought about by different mechanisms, and that the mechanism for perphenazine appeared to be mediated through a pituitary cholinergic system.