Motoyasu Satou

Effect of direct application of estrogen aimed at lateral septum or dorsal raphe nucleus on lordosis behavior: regional and sexual differences in rats.

The role of estrogen in lordosis-inhibiting systems in the lateral septum or the dorsal raphe nucleus was investigated in female and male rats. Ovariectomized rats received implantation of 22-gauge guide cannulae to the bilateral or right side of the lateral septum (LS and rLS, respectively), the dorsal raphe nucleus (DRN) or bilateral cortex (CX). In castrated male rats, bilateral implantations of the cannulae to the LS were carried out (mLS). Three behavioral tests in total were performed at 2-week intervals. In the first test, all animals were subcutaneously injected with 1.5 µg/kg estradiol benzoate (EB). Forty-four hours after EB, 0.5 mg progesterone (P) was injected and a behavioral test was started 4 h after P. These hormonal regimes were used in all tests. In the second test, 2 h before EB injection, 27-gauge cannulae filled with estradiol (E2) were inserted into the DRN, LS or CX through the guide cannulae and were kept there for 4 h. In the third test, cholesterol was implanted instead of E2 into these areas. In the first test, most females showed low levels of lordosis quotient (LQ) and most males showed no lordosis. In the second test, mean LQs in the LS or rLS groups of females increased but not in the DRN and CX groups. In the mLS group no increase of LQ was observed. When cholesterol was implanted in the third test, mean LQs in all groups were as low as in the first test. These results suggest the possibility that estrogen releases the inhibition when it acts on the LS, but not on the DRN female rats. On the other hand, inhibition in the male LS may not be released by the direct action of estrogen.

Lordosis-inhibiting effect of progesterone in female rats with lesions in septum, preoptic area, or dorsal raphe nucleus

Radiofrequency lesions in the septum (SL), the preoptic area (POAL), or the dorsal raphe nucleus (DRL) were made in ovariectomized rats. In a control group of 16 females, ovariectomy, but no brain surgery, was performed. All animals except half of the control rats received injections of 5 mg progesterone (P) 1 h prior to the injection of 5 micrograms/kg b.w. of estradiol benzoate (EB). Instead of 5 mg P, oil was administered to half of the controls. Forty-four hours after EB, all females received 0.5 mg P. A sexual behavior test was performed 4 h after the last injection of P. The result was that oil-treated control rats showed high lordosis quotient (LQ) and soliciting behavior. In contrast, low scores of LQ and no soliciting behavior were observed in all of the 5 mg P-treated rats, even if the SL, POAL, or DRL was made. These results suggest that the septum, the preoptic area, and the dorsal raphe nucleus are not essential for the female sexual behavior-inhibiting mechanisms of progesterone.

Lordosis-inhibiting effect of progesterone in male and female rats with septal lesions.

The inhibitory role of progesterone (P) in regulating lordosis was investigated in male and female rats with septal lesions (SL). Male rats with SL showed lordosis quotients (LQ) as high as female rats with SL and female control rats without brain surgery after injection of 50 microg/kg estradiol benzoate (EB) followed by 0.5 mg P 44 h later. Even when primed with 5 mg P 1 h prior to the 50 microg EB-injection, the mean LQs were still high in all groups. When the dose of EB was decreased to 5 microg/kg, all rats showed high-score LQs. In contrast, all animals in both male and female in which 5 mg P was injected 1 h before 5 microg EB, showed low LQs. These results suggest that P is effective in suppressing lordosis enhanced by estrogen in either male rats or females. Furthermore, the high dose of estrogen overcomes the inhibitory action of P on lordosis in both sexes.

Semi-quantitative analysis for serotonin immunoreactivity and nitric oxide synthase in dorsal raphe nucleus: Effect of estrogen

To know whether GnRH neurons themselves can drive GnRH secretion in a pulsatile fashion, we developed a culture system of olfactory placode. The vomeronasal organ (VNO) was obtained from the embryo of the day 13.5 of gestation and cultured by a roller tube technique. After 2-4 weeks of the culture, the whole amount of medium for each VNO was collected at 8-min intervals over a period of 2 hr. Some VNOs were co-cultured with brain tissues. We found that GnRH secretion in some of VNO cultures, regardless of singleor co-culture, showed a pulsatile fashion (mean pulse interval was 26.8kl.5 min, n=7). Further, treatment with 100 nM of estrogen did not affet this pulsatile GnRH secretion (mean GnRH secretion: control: 0.404kO.072, estrogen; 0.503kO.072, p=O.34), suggesting the absence of negative feedback system of estrogen in the VNO. We coclude that pulsatile GnRH secretion is an intrinsic function of GnRH neurons.

Estrogen in regulating sexual behavior and sex difference

Nuclear receptors for steroids, thyroid hormones, and lipophilic vitamins act as ligand-dependent transcription factors. There are nearly 50 mammalian genes encoding nuclear receptors, but ligands for many have yet to be identified. Among these, the Tlx receptor is characterized by its restricted expression in the CNS, which starts in proliferating neural precursors in the embryonic forebrain, eye, and nasal epithelium and persists at high levels in the adult amygdala and caudate nucleus. Knockout experiments produced viable homozygous mice with reduced rhinencephalic structures associated with aggressive behaviour. Studies in embryos and cell culture indicate that Tlx is involved in regulating the expression of transcription factors such as OtxI and Pax-2, and that overexpression of Tlx appears to confer hyperproliferative properties to neural precursor cells. These observations would help us to uncover a new aspect of genetic programs during forebrain development.

2014 Effect of direct apprication of estrogen into septum or dorsal raphe nucleus on lordosis in female rats

MIWAKO KOIZUMI’ , MASANOBU WATANABE2, HIROYUKI IDE3, KATUYA SEGUR03, SHUICHI KIMURAl Fat digestion is carried out by the concerted action of pancreatic lipase and its protein cofactor, colipase. Colipase is secreted in a precursor form, procolipase. Enterostatin is the N-terminal penta peptide released from procolipase. This penta peptide, named enterostatin, is reported to regulate food intake and specifically inhibit fat preference. To test this hypothesis, the first experiment examined the effect of enterostatin infusion intraperitoneally and into the third ventricle on food intake. It was shown that there was a ruduction in food intake. The subsequent experiment carried on whether enterostatin had an effect on norepinephrin release in the hypothalamus.