The effects of dopamine and D2 receptor antagonists on pituitary hormone secretion are intact in mice lacking dopamine D2L receptor

The dopamine D2 receptor (D2) is involved in the regulation of pituitary hormone secretion. Two isoforms of the D2 receptor, termed D2L and D2S, have been identified. We previously generated D2L knockout mice (D2L-/-), which still express D2S. The present study examined the role of D2S and D2L in spontaneous and drug-induced pituitary hormone secretion. We found that D2L-/- mice had normal serum levels of prolactin and growth hormone. In addition, the antipsychotic drugs haloperidol and clozapine induced a similar dose-dependent increase in serum prolactin in both D2L-/- and wild-type mice. These results suggest that D2S can substitute for the function of D2L in the regulation of pituitary hormone secretion, and that the function of D2S is not dependent on the formation of a receptor heterodimer with D2L.     

Pharmacological evidence that prolactin acts from late gestation to promote maternal behaviour in rabbits

We investigated the role of prolactin and suckling stimulation in the expression of maternal behaviour of primiparous rabbits. Bromocriptine (1 mg/kg/day), given to intact mothers across postpartum days 1-5, decreased serum concentrations of prolactin to undetectable levels, reduced crouching, and increased time inside the nest. Failure of maternal nest-building, provoked by bromocriptine injections from pregnancy day 26 to parturition or to postpartum day 5, correlated with a stronger reduction in crouching and an increased time inside the nest, measures of disturbed maternal behaviour, on postpartum days 3 and 5. Preventing suckling by thelectomy did not prevent prolactin release but reduced crouching incidence and increased the time spent inside the nest on postpartum days 3 and 5. Bromocriptine, injected in thelectomized mothers across postpartum days 1-5, further reduced the incidence of crouching and increased the time spent inside the nest on postpartum days 3 and 5. We conclude that prolactin acting prepartum facilitates maternal behaviour initiation in rabbits and, together with pup stimulation, maintains this behaviour across lactation.     

Helicobacter pylori Containing Only Cytoplasmic Urease Is Susceptible to Acid

Helicobacter pylori, an important etiologic agent in a variety of gastroduodenal diseases, produces large amounts of urease as an essential colonization factor. We have demonstrated previously that urease is located within the cytoplasm and on the surface of H. pylori both in vivo and in stationary-phase culture. The purpose of the present study was to assess the relative contributions of cytoplasmic and surface-localized urease to the ability of H. pylori to survive exposure to acid in the presence of urea. Toward this end, we compared the acid resistance in vitro of H. pylori cells which possessed only cytoplasmic urease to that of bacteria which possessed both cytoplasmic and surface-localized or extracellular urease. Bacteria with only cytoplasmic urease activity were generated by using freshly subcultured bacteria or by treating repeatedly subcultured H. pylori with flurofamide (1 μM), a potent, but poorly diffusible urease inhibitor. H. pylori with cytoplasmic and surface-located urease activity survived in an acid environment when 5 mM urea was present. In contrast, H. pylori with only cytoplasmic urease shows significantly reduced survival when exposed to acid in the presence of 5 mM urea. Similarly, Escherichia coli SE5000 expressing H. pylori urease and the Ni²⁺ transport protein NixA, which expresses cytoplasmic urease activity at levels similar to those in wild-type H. pylori, survived minimally when exposed to acid in the presence of 5 to 50 mM urea. We conclude that cytoplasmic urease activity alone is not sufficient (although cytoplasmic urease activity is likely to be necessary) to allow survival of H. pylori in acid; the activity of surface-localized urease is essential for resistance of H. pylori to acid under the assay conditions used. Therefore, the mechanism whereby urease becomes associated with the surface of H. pylori, which involves release of the enzyme from bacteria due to autolysis followed by adsorption of the enzyme to the surface of intact bacteria (“altruistic autolysis”), is essential for survival of H. pylori in an acid environment. The ability of H. pylori to survive exposure to low pH is likely to depend on a combination of both cytoplasmic and surface-associated urease activities.     

Physiological significance of the negative short-loop feedback of prolactin

The aim of the present study was to evaluate the physiological significance of the rapid, short-loop, negative feedback of prolactin by passive immunization with antiserum to rat prolactin injected into the third cerebral ventricle (3V) of conscious, freely moving intact or castrated male rats. Blood samples for measurement of plasma prolactin concentrations were removed through implanted external jugular catheters. After injection of 3 microliters of undiluted antiserum, plasma levels of prolactin decreased rapidly (within 5 min) to values undetectable by RIA. Further study revealed that this dose of antiprolactin serum had combined with circulating prolactin, thus rendering it undetectable by RIA. To overcome this problem, we repeated the experiment injecting 2 microliters of diluted antiserum (dilution factors 20, 100, 200, 2,000) into the 3V. When compared to values of plasma prolactin in control rats injected with 2 microliters of normal rabbit serum, none of the dilutions of antiserum induced a significant change in prolactin concentrations for as long as 4 h after injection. Since there was no effect of intraventricularly injected antiprolactin serum on basal prolactin secretion, in the next experiment, intact as well as castrated male rats were subjected to ether stress 30 min after intraventricular injection of antiserum (dilution factor 100). The elevation of plasma prolactin which followed ether stress was significantly higher in male rats pretreated with antiprolactin serum than that which occurred in control rats. A similar enhancement of the increase in plasma prolactin following ether stress, but of longer duration, was obtained in castrated rats injected with antiprolactin serum.(ABSTRACT TRUNCATED AT 250 WORDS)     

Radioimmunoassay for human follicle—stimulating hormone: physiological studies

Most of the information concerning secretion changes in follicle-stimulating hormone (FSH) in humans has been gained with relatively insensitive bioassays of concentrates of pools of urine. We have developed a sensitive and specific radioimmunoassay for FSH that is 500-1000 times more sensitive than the rat ovarianweight augmentation assay and which is capable of quantifying FSH in small volumes of serum. Anti-FSH was prepared by immunizing rabbits with an impure FSH preparation. The majority of antisera showed complete inability to distinguish LH, TSH, and FSH, illustrating the immunological similarities of these hormones. One antiserum was specific when used in a radioimmunoassay. Potency estimates by bioassay were in good agreement, with a single exception, with those obtained with the radioimmunoassay for 10 FSH-containing preparations. Highly purified LH gave a higher potency by immunoassay than by bioassay.Sera from eugonadal men contained 5-25 mIU/ml; sera from castrate men contained over 30 mIU/ml. Sera from eugonadal women contained 7-25 mIU/ml during the follicular phase and 5-15 mIU/ml during the luteal phase of the menstrual cycle. Sera from castrate or postmenopausal women contained 40-250 mIU/ml. FSH was measured throughout the menstrual cycle in 19 women. The general pattern that emerged is summarized as follows: there is a small early follicular phase rise in FSH, and then FSH is relatively constant until mid-cycle; in the majority of women a mid-cycle rise of FSH occurs coincidentally to the mid-cycle LH ovulatory peak; during the luteal phase FSH levels are relatively constant and lower than during the follicular phase. Nonsequential oral contraceptives containing estrogen and progestogen abolish these changes and FSH concentrations remain low throughout treatment. Treatment of castrate men and castrate or postmenopausal women with high doses of oral estrogens results in a fall of FSH to levels found in eugonadal men or women, but not to undetectable levels. Children less than 5 yr of age had undetectable FSH (< 5 mIU/ml).