The Effect of Steroids on Sexual Differentiation of the Rat Central Nervous System

Taher, M. Abu (1992) The Effect of Steroids on Sexual Differentiation of the Rat Central Nervous System. MSc(R) thesis, University of Glasgow.

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Abstract

Gonadal steroids have an organisational effect on the sexual differentiation of the mammalian central nervous system. In rodents, sex differences appear to be dependent upon the levels of circulating androgens during a limited perinatal period. Some motor neuron groups in the lumbar and sacral spinal cord exhibit marked sex differences and the number of neurons present are regulated by perinatal androgen levels. These groups include the cremasteric nucleus, the spinal nucleus of bulbocavernosus (SNB) and the dorsolateral nucleus (DLN) which innervate perineal muscles responsible for penile erection and genital reflexes. Muscles are absent and neuron numbers are much reduced in adult females, although they develop similarly in both sexes until birth. There is a considerable body of evidence to show that the normal regression in neuron numbers in females can be prevented by androgen administration during the perinatal period. However, it is less clear whether supplementary androgen treatment given to males at this time can lead to supranormal neuron numbers and the present study uses an unworked strain of rats. Serotoninergic neurons establish contact with these motor neuron groups early in development and the evidence suggests that serotonin suppression also increases the number of surviving neurons. Evidence has come from male or female rodents, while the present study uses males only. The use of 5HT receptor subtype agonists/antagonists in this field is entirely novel. To examine the role of androgens in sexual differentiation of the spinal cord, pregnant female Albino-Swiss rats received 500 Ig per day (administered subcutaneously) of either testosterone propionate (TP) or dihydrotestosterone benzoate (DHTB) during the last four days (17-21) of pregnancy. Alternatively, pups received these treatments for the first four days after birth (200Ig per day subcutaneously). As adults, treated and untreated control males were killed by an overdose of ether and perfused with mammalian Ringer plus lignocaine followed by buffered 10% formalin. The spinal cord was removed by the blow out method and processed. The lumbosacral cord was sectioned at 100 Im on a vibratome and the number of neurons in the SNB, DLN, retrodorsolateral nucleus (RDLN) and ventromedial nucleus (VM) counted after staining with thionine. Untreated control males possessed just under 200 SNB neurons. Motor neuron numbers in males which were treated prenatally with TP and postnatally with DHTB did not differ from controls. However, males which had been treated prenatally with DHTB, or postnatally with TI had significantly raised numbers of motor neurons in the SNB (+15-20%). Males treated postnatally with TP also had significantly raised numbers of motor neurons in the IDLN. Perinatal androgens may thus increase motor neuron numbers in male rodents above normal levels. To examine the role of biogenic amines in sexual differentiation of the spinal cord, male Albino-Swiss rats were given TP (200 ?g/day subcutaneously) on Days 1-3 4-6 and 7-9 postnatally. Controls were left untreated. Half of each group was also injected with the serotonin inhibitor p-Chlorophenylalanine (pCPA) 200 mg/kg intraperitoneally on Days 1-14 after birth. As adualts, motor neuron numbers were counted in the SNB and DLN nuclei. Postnatal androgen and pCPA treatments both significantly raised SNB and DLN neuron numbers in males by some 15-20%. The two treatments did not have an additive effect. Preliminary data suggests that 5HT1 and 5HT2 receptor antagonists also increase motor neuron numbers when they are administered during the postnatal period. For the determination of serotonin and 5 hydroxy indolacetic acid (5HIAA) in the lumbar and thoracic region of the spinal cord of developing Albino-Swiss rats, groups of animals were decapitated on postnatal Days 4, 12, 14 or 22. The spinal cord was removed and separated into lumbar and thoracic parts. The sections were homogenized and centrifuged at 3000 r.p.m. for 10 minutes. Almine concentrations in the resulting supernatant were measured by high performance liquid chromatography with electrochemical detection (HPLC ECD). There were no sex differences in serotonin and 5HIAA concentrations at Day 4 after birth. Sex differences were however present on Day 12. The amount of serotonin in the lumbosacral region of female rats was 0.37ng/mg and in males 0.07ng/mg. The amount of 5HIAA in the lumbosacral region of the female rat was 0.08ng/mg and in the male 0.02ng/mg. Sex differences were also observed on postnatal Day 14. The amount of serotonin in female rats at that time was 0.30ng/mg and in the males 0.07ng/mg. There were no sex differences in 5HIAA content on Day 14. On Day 22 after birth, the serotonin concentration in the lumbar region of female rats was 4.71ng/mg and in the males 4.36ng/mg. The 5HIAA concentration in female rats at the age of 22 days after birth was 1.47ng/mg and in the males 1.40ng/mg. These studies have revealed that perinatal androgen treatment may increase motor neuron numbers. Evidence also suggests that serotonin suppression also increases the number of surviving motor neurons.

Item Type: Thesis (MSc(R))
Qualification Level: Masters
Additional Information: Adviser: D P Gilmore
Keywords: Neurosciences, Endocrinology
Date of Award: 1992
Depositing User: Enlighten Team
Unique ID: glathesis:1992-75300
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 19 Nov 2019 21:17
Last Modified: 19 Nov 2019 21:17
URI: http://theses.gla.ac.uk/id/eprint/75300

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