Human Prostate Cancer

The reproductive organs are not required for an individual's survival but are required for survival of the species. As the individual approaches adulthood, the prostate undergoes developmental changes, resulting in maturation of this gland at puberty. At this stage, the prostate becomes a differentiated gland that produces proteins and other substances fundamental for reproduction and survival of the species. By the age of 50, as many as 30 of all men will harbor microscopic foci of prostate...

Rodent Prostate Cell Differentiation

Biochemical analysis exists on the rat prostate, but limited information is published on the secretory proteins of the mouse prostate. Also, no rodent analog for human PSA has been identified. The rat ventral lobe differs most significantly from the other lobes because its protein products are quite distinct (101-103). The rat anterior lobe produces many of the androgen-regulated proteins seen in the dorsolateral prostate (104). The seminal-vesicle secretion II (SVSII) is a major secretory...

Hematopoiesis and Immune Function

Several observations have contributed to the idea that prolactin may be an important regulator of hematopoiesis and immune function in mammals. First, both the prolactin receptor and ligand have been identified in cells of the hematopoietic system (52-56). Second, pharmacological studies in animals and clinical correlations in humans have shown that prolactin alters parameters of hematopoiesis and immune function (57-61). Third, certain cells cultured from hematopoietic lineages respond to...

Transgenic And Knockout Animals In Studies Of Food Intake Body Composition And Obesity

In addition to the studies of GH described earlier in this chapter, transgenic and targeted gene-disruption technologies are used to elucidate the mechanisms controlling food intake, body composition, and the pathogenesis of obesity. Within the past few years, the applications of these genetic techniques in whole animals have identified a number of new molecules and physiologic pathways involved in the regulation of body wt, and have led to important new insights into the pathophysiology of...

MISDeficient Mice Lossof Function Study

Wolffian Structures

From the gain-of-function study described in the previous section, we have learned what MIS can do during male and female sexual differentiation. It is also important to Summary of Gain- and Loss-of-Function Studies of MIS MIS-overexpressing Externally female Impaired development of the Wolffian duct Undescended testes Fewer germ cells Presence of uteri Majority infertile Hyperplasia of Leydig cells Testicular atrophy Presence of uteri Majority infertile Hyperplasia of Leydig cells Testicular...

References

Oestrus, ovulation and menstruation. Physiol Rev 1923 111 457-482. 2. Frobenius W. Ludwig Fraenkel 'spiritus rector' of the early progesterone research. Eur J Obstet Gynocol 1999 83 115-119. 3. Corner GW, Allen WM. Physiology of the corpus luteum II. Am J Physiol 1929 88 326-339. 4. Allen WM. Physiology of the corpus luteum V. Am J Physiol 1930 92 174-188. 5. Csapo A. Progesterone. Sci Am 1958 198 40-46. 6. Pincus G. Steroid labile reproductive processes in mammals. Harvey Lect....

Trophic Factors for Gonadotropes and Thyrotropes

Although not a transgenic model, the hpg mouse is particularly relevant to this topic. These mice harbor a spontaneous deletion of at least 33.5 kb (96) from chromosome 14 (97) removing the distal portion of the gene encoding a biosynthetic precursor of both gonadotropin-releasing hormone (GnRH) and GnRH-associated peptide (GAP) (96). Although the mice are capable of expressing mRNA from the truncated gene, no synthesis of GnRH or GAP occurs. Following the loss of this hypothalamic trophic...

Igf2 And Igf2 Receptor

Igf2 was the first member of the insulin Igf family to be knocked out, now almost a decade ago (31). This experiment revealed that murine Igf2 expression is subject to genomic imprinting, and that gene is expressed from the paternal allele. As a result, deletion of the paternal allele results in dwarfism, while deletion of the maternal allele has no apparent effect (31,32). Igf2 p- + and - - are indistinguishable, and dwarfism is apparent shortly after placentation (31,32). These mice are...

Antral Follicle Development Sensitivity To Extra Ovarian And Intra Ovarian Regulation

During follicular development in mice, follicular antrum formation represents a transition from primarily intrafollicular regulation to a combination of intraovarian and extraovarian regulation. Follicles enter a rapid period of growth, and synthesize peptide and steroid hormones that impact on the reproductive axis. Multiple positive and negative feedback loops between the hypothalamus, pituitary, and ovaries coordinate follicle maturation with sexual behavior and physiological preparation for...

Role Of Kit Ligand In Female Gametogenesis

In female embryos, once PGCs have entered the fetal ovary, they complete mitotic divisions and enter meiosis. They eventually arrest meiosis at Prophase I, and each germ cell will become invested by a layer of flattened somatic cells that are the precursors of the follicle or granulosa cells. Therefore, in the ovary, just as in the testis, germ-cell survival, growth, and differentiation is controlled by the complex interaction between the germ cells and the surrounding somatic cells (62,63)...

StAr Knockout Mice

As shown in Fig. 1, one essential step in steroidogenesis is the translocation of cholesterol from the cytoplasm to the inner mitochondrial membrane, where the cholesterol side-chain cleavage enzyme (P450scc) catalyzes the first committed reactions in steroidogenesis. The steroidogenic acute regulatory protein (StAR), a 30-kDa mitochondrial phosphoprotein, was initially isolated because its expression within steroidogenic cells was rapidly induced by trophic hormones (3). These findings...

Inhibin Activin And Follistatin Deficiency Or Overexpression

While GnRH pulsatility provides one mechanism for differential FSH and LH regulation, other factors are clearly involved. A myriad of in vivo and in vitro studies clearly indicate a role for activins, inhibins, and follistatins in the selective regulation of FSH (3). As their names suggest, activins stimulate, while inhibins attenuate FSH synthesis and secretion. Both activins and inhibins are members of the transforming growth factor-p (TGFP) protein family. Activins are comprised of two...

Kit Ligand In Germline Development

The infertility seen in many W and Sl mutants signifies the important role played by this signaling pathway in germline development. A growing body of evidence suggests that c-kit receptor and its ligand function at different times during the development of the germline. Moreover, the function of this signaling pathway appears to vary depending on the cell type and stage of development in which the receptor or ligand is expressed. The first stage at which these mutants affect germ-cell...

Toxigenic Ablation Of Melanotrophs And Corticotrophs

Ablation of selected cell populations in transgenic mice using a targeted toxigenic protein has been useful in cell-lineage studies and physiological studies of tissue function within a complex biological environment 58-61 . The two most commonly used toxins have been diptheria toxin A chain DTA and herpes simplex virus type 1 thymidine kinase HSV1-TK , although both have limitations. HSV-TK has the advantage of temporal control, because its toxicity in most mammalian cells is dependent on...

Control of Embryonic Development

Fat Pad Disruption

In comparison to postnatal mammary gland development, very few knockout or transgenic mice have been reported to have defects in embryonic development. Some of the genes implicated in embryonic mammary development are presented in Fig. 4. Presumably, disruption of genes that mediate epithelial-mesenchymal interactions would result in embryonic defects. Two such mouse models have been reported, p63 - - 45,46 and lymphoid-enhancer factor Lef -1 - - 47 mice. p63, a homolog of the tumor-suppressor...