199 Nearly fifteen hundred years ago. For Aristotle on the effects of castration see his Historia animalium in Complete works volume 1 pp.981–2. For a more recent view of the same subject see Wilson and Roehrborn (1999).
203 We think of the estrogens. For estrogen-receptor deficiency (133430) in men see Smith et al. (1994). The enzyme that converts testosterone to estrogen is aromatase cytochrome P450 (107910) For loss-of-function mutations that cause continued growth in men see Sharpe (1998); Lee and Witchel (1997); for gain-of-function mutations that cause excess in women see Stratakis et al. (1998).
203 Growth hormone and IGF are extremely powerful. One of the several cancer-predisposition syndromes caused by mutations in PTEN (601728) is Cowden syndrome (158350). For the evidence that Proteus syndrome (176920) is also caused – at least sometimes – by PTEN loss-of-function mutations see Zhou et al. (2000, 2001). The Ovid quote is from Metamorphoses (trans. A.D. Melville. 1986. Penguin Books, Harmondsworth, UK). Seward (1992) re-examines Joseph Merrick’s skeleton in detail and upholds the traditional diagnosis of neurofibromatosis type 1 (162200). Tibbies and Cohen (1986), Cohen (1988) and Cohen (1993), however, argue for Proteus syndrome.
206 The intimate relationship between growth and cancer. For the relationship between IGF titres and dog body-size see Eigenmann et al. (1984, 1988); Eigenmann (1987). The association between osteosarcoma and size in dogs was detected by Tjalma (1966), in children by Fraumeni (1967). The latter result has been confirmed by three out of four studies since. See Leroi et al. (2003) for a general discussion on the causes of pediatric cancers. Jenkins (1998) reviews increased propensity of acromegalics to a variety of cancers. The causal role of IGF is reviewed by Holly et al. (1999). In his classic book on ageing, Comfort (1964) first noted that big dogs do not live as long as small dogs. See also Patronek et al. (1997) and Miller and Austad (1999). The best data on ageing rate, from the Swedish pet health insurance scheme, is given in Egenvall et al. (2000).
208 I am fascinated by these findings. Krzisnik et al. (1999) discuss the dwarfs of Krk who are homozygous for recessive mutations in PROP-I. Samaras and Elrick (1999) and Samaras et al. (1999) give a partisan account of the evidence for a negative association between human height and longevity. See Waaler (1984) and Power and Matthews (1997) for the general positive association between health and longevity. There is, however, some evidence from the Finnish studies of a U-shaped mortality distribution in women, possibly associated with skeleto-muscular problems in the tallest women (Läärä and Rantakallio 1996; Silventoinen et al. 1999).
208 These results seem to tell us. The first dwarf mice which were shown to be long-lived were Snell dwarfs (dw) which are deficient in a number of their pituitary gland lineages because of a mutation in PIT-I, a pituitary specific transcription factor. Ames dwarf (dj)has the same phenotype, but has a mutation in another transcription factor, PROP-I. Both these mice are long-lived, but since they lack both somatotrophs and thyrotrophs, they fail to produce both growth hormone and thyroid-stimulating hormone, making it impossible to distinguish the effects of lacking either (Brown-Borg et al. 1996; Bartke et al. 2001 a; b). However, the Little mouse (lit) is also long-lived (Flurkey et al. 2001). Since this dwarf mouse has a mutation in its growth-hormone releasing-hormone receptor (GHRHR), it is very likely that it is growth-hormone deficiency, or its sequelae, that cause the longevity of these strains.
209 To be poor is to be both short and at higher risk. See Mansholt (1987) on Dutch growth; Mackenbach (1991) on the socio-economic causes of height differences in Holland and Didde (2002) for height-related activism in the Netherlands. Also see Cavelaars et al. (2000) for a fascinating comparision of the secular increase in all European countries which shows that although all countries show a secular increase in height, they are all getting taller at more or less the same rate. There is much evidence that milk consumption is responsible for a good deal of environmental variation in height, for example, in the Japanese; Takahashi (1984); Bogin (1999a) p.268.
210 The poverty and short stature of the north’s people. See Rosenbaum et al. (1985) and Mascie-Taylor and Boldsen (1985) for regional differences in height in England and Townsend et al. (1992) for the authoritative survey of health inequalities in Britain. Tanner (1981) p.147 discusses Chadwick and his surveys of height.
211 It is precisely the antiquity of the positive association. There is a huge literature on the attractions of height. Some of it reviewed by Bogin (1999a) pp.326–7. See Sandberg et al. (1994), Guyda (1998) and Root (1998) on growth-hormone therapy for short children.
CHAPTER VII: THE DESIRE AND PURSUIT OF THE WHOLE
217 In February 1868, a Parisian. For the journal and other relevant papers see Barbin (1980). Confusingly, Herculine Adélaïde (Alexina) refers to herself as ‘Camille’.
221 Is Alexina a woman? Chesnet (1860) Annales d’hygiène et de médecine légale 2e série, XIV: 206 quoted in pp.124–8 of Barbin (1980). See Goujon (1869) for her autopsy. See Dreger (1998) for a social history of hermaphrodites.
223 Anatomists, however, have other tastes. Laqueur (1990) claims that Vesalius’ and Galen’s homologies are confirmed by modern, or rather nine-teeth-century, embryology, but this is not so. Thiery and Houtzager (1997) p.51 describe the background of Vesalius’ analysis of the vagina and note that Vesalius so loved his homology between the uterus and scrotum that he depicted the former with a dividing cleft comparable to the raphe of the scrotum where there is none.
225 It was another Paduan anatomist. Laqueur (1989) delves deeply into the history of the identity of male and female genitalia. O’Connell et al. (1998) redescribe the vestibular bulbs as the clitoris; Williamson and Nowak (1998) add further details about the discovery; Kobelt (1844) gives an earlier view.
228 By day 28. Descriptions and timing of embryological events are from McLachlan (1994). I have omitted a description of the internal genitalia (fallopian tubes, uterus and upper vagina, epididymus, vasa deferentia and seminal vesicles), all of which have other embryological origins and are controlled by other hormones.
230 To develop as a female is to travel. For an account of the discovery of the Y see Mittwoch (1973); XX[n]Y males are also often mentally retarded and sterile. The condition is known as Kleinfelter syndrome and occurs a frequency of 1 in 1000 male births (Conner and Ferguson-Smith 1993).
231 The search for the source of the Y’s power. The papers that describd SRY (480000) in humans and mice are Sinclair et al. (1990); Gubbay et al. (1990); McLaren (1990) gives a contemporary commentary.
233 Perhaps SRY activates a few critical genes. For an update of the genes known to be regulated by SRY in the gonad see Graves (1998). For Alexandre Jost’s experiments see Jost (1946–47). The results described are true for rabbits castrated before day 22 post coitem.