No abstract

Sexual behavior was observed in male mice that were homozygous for a null mutation of the c-fos proto-oncogene, as well as in heterozygous mutants and wild-type controls. The onset of mounting was slower and the subsequent mounting rate was significantly lower in homozygous mutants than in either group of controls. Even so, a similar percentage of males of each genotype achieved ejaculation, and ejaculation latencies were equivalent in these mice. Likewise, in males that intromitted, the intromission efficiency and the number of intravaginal thrusts/intromission were similar among the three genotypes. The nuclear protein product (Fos) of c-fos was visualized immunocytochemically in the brains of heterozygous male mice 1 h after they exhibited a series of mounts, with or without intromission, leading to an ejaculation. As in the male of several other rodent species, nuclear Fos immunoreactivity was augmented in neurons of limbic and midbrain regions thought to convey olfactory/vomeronasal and genital/somatosensory information, respectively, to the medial preoptic area following contact with an estrous female. One interpretation of our behavioral results is that in the absence of normal neuronal c-fos expression, sensory stimuli that impinge on the male brain during mating lose their ability to initiate a cascade of further gene transcription events that otherwise control the rate at which a male reorients towards and mounts an estrous female during an ejaculatory series. Alternatively, the c-fos null mutation may disrupt normal neural development, leading to a structural change that mediates the observed deficit in mounting capacity.

SUMMARY Dose-response curves relating plasma angiotensin II (AH) concentration during AH infusion to blood pressure (BP), to plasma aldosterone, and to plasma 18-hydroxycorticosterone were compared in normal subjects and in patients with essential hypertension, Conn's syndrome, and nontumorous hyperaldosteronism. The BP response was steeper than normal in patients with Conn's syndrome and essential hypertension. Before infusion, mean plasma aldosterone concentration was approximately four-fold higher in Conn's syndrome than in the normal group, while that of 18-hydroxycorticosterone was ninefold higher. Neither increased significantly during AH infusion. In essential hypertension, both corticosteroids were within the normal range, but their responses to AH infusion were greater than normal. In the three subjects with nontumorous hyperaldosteronism, plasma aldosterone and 18-hydroxycorticosterone concentrations were raised, and their responses to AH infusion resembled those found in essential hypertension and were different from those found in Conn's syndrome. This suggests that nontumorous hyperaldosteronism is not a rariant of Conn's syndrome. In the response to AH and in other ways, it is indistinguishable from essential hypertension. a benign adrenocortical adenoma (Conn's syndrome), notably ACTH, sodium, and potassium, and hyperaldosteronism associated with bilateral determine the secretion rate and plasma micronodular hyperplasia of the adrenal cortex (nonconcentration of aldosterone in humans, angiotensin tumorous hyperaldosteronism). 2 Data on the behavior II (All) is probably the most important. Angiotensin of 18-hydroxycorticosterone in plasma in these II also raises the plasma concentrations of 18-categories are sparse. The present study compares the hydroxycorticosterone, the probable immediate preeffect of All infusion on plasma concentrations of cursor of aldosterone, but is unimportant in conaldosterone and 18-hydroxycorticosterone in groups trolling the plasma levels of other corticosteroids. In of subjects with these forms of hypertension to its normal subjects, the relationship between plasma All effect in normal subjects, and aldosterone levels can be altered, for example, by sodium depletion or loading: the effect on plasma 18-hydroxycorticosterone concentration is less clear but may also change in this way (see review 1). Methods The All: aldosterone relationship may differ from All subjects were studied under identical conditions normal in some types of hypertension, including essen-, n a metabolic ward. For 5 to 6 days before the study, tial hypertension, primary hyperaldosteronism due to they ate a fixed diet containing between 145 and 155 mEq sodium and between 50 and 80 mEq potassium daily. Angiotensin II (Hypertensin, Ciba) was infused

The converting enzyme inhibitor enalapril, in single daily doses of 10-40 mg, was given to 20 hypertensive patients with renal artery stenosis. The blood pressure fall six hours after the first dose of enalapril was significantly related to the pretreatment plasma concentrations of active renin and angiotensin II and to the concurrent fall in angiotensin II. Blood pressure fell further with continued treatment; the long term fall was not significantly related to pretreatment plasma renin or angiotensin II concentrations. At three months, 24 hours after the last dose of enalapril, blood pressure, plasma angiotensin II, and converting enzyme activity remained low and active renin and angiotensin I high; six hours after dosing, angiotensin II had, however, fallen further. The rise in active renin during long term treatment was proportionally greater than the rise in

The ontogeny of hyaluronan (HA) secretion during early mouse embryogenesis has been investigated using a biotin-labelled HA-binding complex from cartilage proteoglycan. HA is first secreted by visceral endoderm cells of the early egg cylinder on day 5.5 post coitum (p.c.), predominantly into the expanding yolk cavity. On day 6.5 p.c., HA is present in both the yolk and proamniotic cavities, but pericellular staining is restricted to the visceral endoderm and a population of embryonic ectoderm cells at the antimesometrial end of the proamniotic cavity. By the primitive streak stage, HA is secreted into the ectoplacental, exocoelomic, amniotic and yolk cavities, whilst the only cells exhibiting pericellular staining are those of the embryonic and extraembryonic mesoderm, including the allantois. Comparisons of HA-staining patterns of cultured whole blastocysts, microdissected trophectoderm fragments and immunosurgically isolated inner cell masses, revealed no trophoblast-associated HA secretion during outgrowth in vitro but significant synthetic activity by the endodermal derivatives of differentiating inner cell masses. To identify the cell lineages responsible for secretion of HA into the embryonic cavities and to investigate the origin of the HA observed around migrating mesoderm cells, day 7.5 p.c. primitive streak stage conceptuses were dissected into their various embryonic and extraembryonic cell lineages. HA secretion was observed after short-term suspension culture of mesoderm, embryonic ectoderm and embryonic endoderm, but was undetectable in fragments of ectoplacental cone, parietal yolk sac (primary giant trophoblast and parietal endoderm), extraembryonic ectoderm or extraembryonic endoderm. The level of synthesis by the HA-positive tissues was markedly enhanced by culture in medium containing serum, compared with that obtained following culture in medium supplemented with a defined serum substitute containing insulin, transferrin, selenous acid and linoleic acid. This suggests that additional growth factors, present in serum but absent from the serum substitute, are required for optimal HA synthesis by the HA-secreting tissues in vitro, and probably also in vivo. The implications of these events for implantation and the development of peri- and early post-implantation mouse embryos are discussed, and a new role for HA in the initial formation and expansion of the embryonic cavities is proposed.