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Summary.
Comparisons were made of the sexual behaviour of sham-operated male hamsters and castrated males receiving testosterone, dihydrotestosterone or androstenedione (1·5 mg/week), or oil alone. Tests of short duration (10 min) were conducted at Week 3 (when the animals were sexually naive), Week 6 and Week 9. Sham-operated males showed marked increases in many elements of behaviour between Weeks 3 and 9, while castrated males receiving no androgen replacement showed marked decreases. Males receiving each of the three androgens showed marked increases in behaviour, but androstenedione-treated males showed less facilitation of sexual behaviour than controls. Dihydrotestosterone was as effective as testosterone. The three androgens were comparable in maintaining seminal vesicle weight after castration and in preventing the customary rise in pituitary and body weights. These data suggest that, unlike the situation in the rat, aromatization of androgens is unnecessary for the display of sexual behaviour in the hamster.
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Adult female hamsters were treated with a long-acting form of morphine before mating and throughout pregnancy; the drug was gradually withdrawn during lactation. The offspring produced were gonadectomized as adults and tested for their ability to display feminine and masculine sexual behaviour after appropriate hormonal priming. Chronic exposure to morphine during development resulted in males that showed an increase in both feminine and masculine sexual behaviour when compared with controls.
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Summary. Female Albino Swiss rats were exposed to 5α-dihydrotestosterone benzoate (DHTB) for the last 4 days of gestation, or for 4 days after birth, or both. Post-natal DHTB exposure (as well as pre- plus post-natal exposure) resulted in a 2–3-fold increase in the number of motor neurones forming the spinal nucleus of bulbocavernosus (SNB); numbers were intermediate between those found in normal females (∼40) and males (∼200). These DHTB-treated groups also possessed perineal muscles which were ∼25% of the weight of those in normal males. Transverse sections of one of the muscles (levator ani) showed that it had approximately half the muscle fibres of normal males. Females exposed prenatally to DHTB showed a small (but significant) rise in SNB numbers, but had no recognizable perineal muscles.
Keywords: neonate; motor neurones; hormones: perineal muscles; rat
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Summary. Newborn female Albino Swiss rats received testosterone propionate, dihydrotestosterone benzoate or oestradiol benzoate for 4 days after birth. The neonatal administration of all three hormones maintained neurones of the spinal nucleus of bulbocavernosus (SNB) complex in adulthood at levels intermediate between those found in normal females (∼40 neurones) and those found in normal males (∼220 neurones). Dihydrotestosterone benzoate was the most effective treatment. Oestradiol benzoate, while as potent as testosterone propionate in maintaining SNB neurone numbers, could not maintain the perineal muscles which are their normal target. Dihydrotestosterone benzoate and testosterone propionate maintained both neurones and muscles.
Newborn male Albino Swiss rats received either the aromatase inhibitor 4-OH-androstenedione, or the 5α-reductase inhibitor aza-steroid 17β-N,N-diethylcarbamoyl-4-methyl-4-aza-5α-androstan-3-one (4-MA). Only neonatal treatment with 4-MA led to reduced SNB neurone numbers in adulthood, but the reduction was modest (−16%). The results of the two experiments suggest that several hormones can maintain SNB neurone numbers in Albino Swiss rats, but that 5α-reduced metabolites of testosterone may be particularly effective.
Keywords: neonate; motor neurones; hormones; perineal muscles; rat
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Intrauterine infection and inflammation are responsible for the majority of early (<32 weeks) spontaneous preterm births (PTBs). Anti-inflammatory agents, delivered intra-amniotically together with antibiotics, may be an effective strategy for preventing PTB. In this study, the effects of four cytokine-suppressive anti-inflammatory drugs (CSAIDs: N-acetyl cysteine (NAC), SB239063, TPCA-1 and NEMO binding domain inhibitor (NBDI)) were assessed on human and ovine gestational membrane inflammation. Full-thickness membranes were collected from healthy, term, human placentas delivered by Caesarean section (n=5). Using a Transwell model, they were stimulated ex vivo with γ-irradiation-killed Escherichia coli applied to the amniotic face. Membranes from near-term, ovine placentas were stimulated in utero with lipopolysaccharide, Ureaplasma parvum or saline control and subjected to explant culture. The effects of treatment with CSAIDs or vehicle (1% DMSO) on accumulation of PGE2 and cytokines (human interleukin 6 (IL6), IL10 and TNFα; ovine IL8 (oIL8)) were assessed in conditioned media at various time points (3–20 h). In human membranes, the IKKβ inhibitor TPCA-1 (7 μM) and p38 MAPK inhibitor SB239063 (20 μM) administered to the amniotic compartment were the most effective in inhibiting accumulation of cytokines and PGE2 in the fetal compartment. NAC (10 mM) inhibited accumulation of PGE2 and IL10 only; NBDI (10 μM) had no significant effect. In addition to the fetal compartment, SB239063 also exerted consistent and significant inhibitory effects in the maternal compartment. TPCA-1 and SB239063 suppressed oIL8 production, while all CSAIDs tested suppressed ovine PGE2 production. These results support the further investigation of intra-amniotically delivered CSAIDs for the prevention of inflammation-mediated PTB.
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Luteolysis in sheep is associated with uterine secretion of pulses of prostaglandin F2α (PGF2α) due to the action of luteal oxytocin on endometrial oxytocin receptors. For pregnancy to become established inhibition of oxytocin receptors is important as an antiluteolytic mechanism. The maternal recognition of pregnancy in cattle and sheep involves production, by the trophoblast, of a type 1 interferon (IFN-τ) that suppresses uterine development of oxytocin receptors and the generation of luteolytic episodes of PGF2α. The action of IFN-τ in surgically prepared unilaterally pregnant ewes was investigated. Finn–Dorset ewes were anaesthetized on day 6 or 7 of the oestrous cycle and one uterine horn was surgically isolated at the uterine bifurcation from the body of the uterus. Ewes were mated at the subsequent oestrus either by a fertile or by a vasectomized ram and killed on day 13 or 16 after mating. On day 16, in the non-pregnant ewes, there was no measurable uterine IFN-τ but there were high concentrations of oxytocin receptors in both horns. In the pregnant ewes, on day 16 after mating, the oxytocin receptor concentration was 45 ± 11 fmol mg−1 protein in the pregnant horn and 585 ± 131 fmol mg−1 in the non-pregnant horn. Antiviral activity was 5.8 × 107 ± 5.2 × 107 U ml−1 in the pregnant horn and 2.9 × 103 ± 1.2 × 103 U ml−1 in the non-pregnant horn. Thus, 16 days after mating, the pregnant horn exhibited high antiviral activity but oxytocin receptors were suppressed, while in the same endocrine environment (characteristic of pregnancy) there were low IFN-τ and high oxytocin receptor concentrations in the isolated horn equivalent to those expected at the onset of luteolysis. In situ hybridization to ovine mRNA encoding the oxytocin receptor and autoradiographic studies using the125I-labelled oxytocin antagonist d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH2 9]-vasotocin both showed that the large amount of oxytocin receptor message and binding sites in the endometrium of the isolated horn were localized in the luminal epithelium. Immunocytochemical studies showed that there was a suppression of oestradiol receptors in the pregnant horn but high concentrations equivalent to those at oestrus were present in the isolated horn. The content of progesterone receptors was low in the stromal tissue only in both horns, a pattern of localization similar to that seen in the late luteal phase and in early pregnancy. These results are consistent with a local action of IFN-τ on endometrial oxytocin receptors and endometrial oestrogen receptors; they raise the possibility that reduced oestrogen receptor function mediates the inhibitory effect of IFN-τ on oxytocin receptor expression, but the exact relationship between the suppression of oestradiol and oxytocin receptors in relation to the antiluteolytic action of IFN-τ requires further study.
