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Item The effect of estrogen and progesterone on sex differences in susceptibility to noise[-]induced hearing loss : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Occupational Health and Safety at Massey University, Manawatu, New Zealand(Massey University, 2013) Hislop, Renee AdeleThere is some evidence suggesting that males and females differ in susceptibility to noise induced hearing loss (NIHL): that is, they differ in NIHL magnitude even when exposed to the exact same noise exposure (1, 2), and that this may be related to the effects of circulating levels of the female sex hormones estrogen and progesterone on the cochlear response to noise (3-8). The main objective of this research was to determine what effect estrogen and progesterone levels had on sex differences in susceptibility to human temporary threshold shift (TTS) and otoacoustic emission (OAE) shift. A secondary objective was to determine whether estrogen and progesterone levels impacted on the prediction of susceptibility to NIHL using measures of auditory physiology: OAE amplitude, efferent suppression magnitude and 4 kHz pure tone audiometry thresholds. Additionally, it was determined whether the female sex hormones acted to influence susceptibility to NIHL via their effect on these measures of auditory physiology or whether hormones acted independently of these effects to influence susceptibility to NIHL. 25 female and 21 male participants aged 18-35 were exposed to a 3 kHz, continuous, pure-tone noise exposure at 100 dB LAeq for 15 minutes in their right ear. This exposure provided the equivalent energy to an eight-hour continuous A-weighted sound pressure level, LAeq,8h of 85 dB. To address the main objective TTS, OAE shift and recovery from TTS and OAE shift were compared in males and females. Serum levels of estrogen and progesterone were measured in female participants and correlations were made between these levels and TTS and OAE shift data. To address the second objective correlations were calculated between auditory physiology measures, TTS and OAE shift for males and females as well as between the sex hormones and auditory physiology measures. Additionally, linear regression models were produced to assess the mediating role of the auditory physiology measures on the relationship between hormones TTS and OAE shift. This research found no difference between males and the entire group of females in susceptibility to TTS, OAE shift or recovery from OAE shift, although females had a slower recovery from TTS. However, when circulating levels of estrogen and progesterone levels were accounted for a sex difference in TTS was apparent. This difference was driven by a large, significant, negative correlation between progesterone levels and TTS, whereas estrogen had no significant correlation with TTS or OAE shift. However, estrogen mediated different aspects of auditory physiology, whereas progesterone did not. There was no interaction between the effects of estrogen and progesterone on TTS or OAE shift. Additionally, there was a mediating role of some aspects of auditory function on the effects of estrogen on TTS and to a greater degree on OAE shift. However, estrogen itself only had a small non-significant impact on TTS and OAE shift so this suggests that the impact of auditory function and hormones on TTS and OAE shift are independent.Item Mammogenesis in the mouse : a study of the responses of the immature mammary gland to minimal oestrogenic stimulation : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy at Massey University(Massey University, 1979) Aye, Khin MaungThe response of the mammary glands of immature ovariectomized mice of the NOS strain to minimal levels of oestradiol monobenzoate was investigated in two experiments using both objective and subjective measurements as indices of response. Uterus weight, thickness of the uterine wall and vaginal opening were used as additional measures of the effectiveness of the oestrogenic stimulation. In the first experiment single injections of OMB at four levels (0.01, 0.03, 0.09 and 0.27µg) were used and mice were killed at four intervals after the injection (1,2,4 and 8 days). A significant dose response relationship was observed for mammary gland area to OMB which was essentially linear. Different stages of the response were observed both with respect to the morphology (in whole mounts) and the micro-anatomy (in serial histological sections) of the duct system. The sampling errors of a histometric estimate of volume of glandular tissue were investigated and the results used to design a stratified sampling system for the second experiment. In the second experiment dual injections at one of three levels (0.04, 0.1 and 0.2µg total), given at one of three spacings (2, 4 and 8 days) were used and mice were killed at one of three intervals after the second injection (2, 6 and 14 days). The response of the mammary gland to log-dose of OMB was essentially linear for the estimate of volume of glandular tissue, but no response to increasing level of OMB was seen with mammary gland area. The detailed observations of the morphological and histological changes have been discussed in relation to the results reported in other studies. The following stages have been proposed as the sequence of events, which can extend over a period greater than a week, following discrete doses of oestrogen at minimally effective levels: (1) Increase in width of principal ducts, thickening of the epithelial wall and the appearance of a non-specific secretion: (2) Formation of peripheral 'clubs' accompanied by mitotic activity along the length of the principal ducts; (3) Extension of the principal ducts from the peripheral clubs and formation of small end buds at discrete points along the principal ducts. (4) Extension of the small end buds to form higher order duct branches.