Lecture
Outline #6: Pituitary Hormones
(pituita = phlegm, thus the pituitary was first thought to filter waste from the 3rd ventricle of the brain and transfer it to the nasal sinuses as phlegm.)
I. THE CONSEQUENCES OF HYPOPHYSECTOMY (first by Philip Smith, 1927-28)
In realizing the importance of the pituitary, Smith stated, "Hypophysectomy in the rat gives an invariable syndrome, the main features of which are: an almost complete inhibition in growth in the young and a progressive loss of weight in the adult, an atrophy of the genital system with a loss of libido sexualis, and in the female, a cessation of sexual cycles; an atrophy of the thyroids, parathyroids and suprarenal cortex; and a general physical impairment characterized by a lower resistance to operative procedures, loss of appetite, weakness and a flabbiness that readily distinguishes the hypophysectomized animal from the normal animal. It seems unlikely that they can live a normal life-span." (Pronunciation of “hypophysectomy.”)
II. DEVELOPMENT OF THE ANTERIOR AND POSTERIOR HYPOPHYSES (Figs. 5.2.a & 5.2.b)
(Note: to see the fully developed pituitary, click on Fig. 5.3.)
1. Adenohypophysis (anterior pituitary) differentiates from Rathke's pouch, an outgrowth of epithelial tissue from the roof of the embryonic mouth. (Fig. 5.4)
2. Neurohypophysis (posterior pituitary) evaginates from the diencephalon, a part of the primitive forebrain that arises from the neural ectoderm. (Fig. 5.5)
III CELLULAR
COMPOSITION AND HORMONES OF THE ADENOHYPOPHYSIS
1. Acidophils produce the larger "direct acting" hormones: (a) somatotropes (which secrete SH) constitute half of the adenohypophyseal cells; (b) mammotropes (i.e., lactotropes) (which secrete PRL) are the second most abundant type of cell in the adenohypophysis.
2. Basophils produce the trophic hormones (i.e., glycoprotein hormones) which stimulate other glands to secrete hormones such as steroids. (trophic = increasing the activity of): (a) thyrotropes secrete TSH, gonadotropes secrete FSH and LH, and corticotropes secrete ACTH (and proopiomelanotropin)
3. Chromophobes have no stainable granules and their function is unclear. They may: (a) be supportive tissue, (b) be stem cells for acidophils and basophils, or (c) be associated with ACTH secretion.
IV. SECRETION AND ACTION OF ADENOHYPOPHYSEAL HORMONES
A. THE MAJOR BODY GROWTH-PROMOTING HORMONES
1. Somatotropin (SH) (AKA = growth hormone (GH), somatotropic hormone (STH))
a. SH & PRL are both alpha-helical polypeptide chains of ~191 amino acids.
b. Somatocrinin (an SH-releasing hormone) from the hypothalamus may promote SH secretion.
c. SH increases during sleep, stress, high estradiol, low blood glucose, or protein depletion.
d. Most of the daily secretion is during the first 90 min of sleep (e.g., see Figure 5.6 in text).
e. SH increases the size of skeleton, muscle, and connective tissues.
f. SH acts by stimulating protein synthesis in these tissues within 30 min.
g. SH secretion is inhibited by somatostatin (a.k.a. SRIF, or somatotropin-release inhibiting factor).
2. Prolactin (PRL) (AKA lactogen, lactogenic hormone, mammotropin)
a. A hypothalamic-releasing factor for PRL has not been identified (TRH, may promote its release.)
b. Alternatively, PRL secretion may be controlled by a pituitary inhibitory substance, i.e., a PIF, from the hypothalamus; or, possibly by hypothalamic dopamine, a simple derivative of tyrosine.
c. PRL was first characterized for its ability to initiate lactation. It stimulates receptors in mammary glandular cells to take up glucose and synthesize fat, casein, lactalbumin, and lactose.
d. PRL decreases within 3 weeks after parturition, if the mother does not nurse.
B. THE GLYCOPROTEIN HORMONES
(NOTE: Glycosylation probably protects a hormone from proteolytic degradation, but these carbohydrate moieties also appear to be important for coupling with the hormone receptor because if you deglycosylate a glycoprotein hormone it can act as an antagonist rather than an agonist.)
1. Thyrotropin (AKA, thyroid stimulating hormone, or TSH)
a. TSH stimulates the thyroid gland to secrete T3 and T4.
b. TSH is controlled by: (Fig. 13.9)
(i) CNS input to the hypothalamus to secrete thyrotropin-releasing hormone (i.e., TRH)
(ii) T3 and T4 feedback inhibition of TRH secretion
(iii) T3 and T4 feedback inhibition of thyrotropes (and TSH secretion).
2. Luteinizing Hormone (LH, or lutropin)
a. LH stimulates progesterone synthesis, ovulation, and luteinization of the female ovarian follicles, and stimulates testosterone production by the interstitial cells of the male gonads.
b. LH production is regulated by hypothalamic GnRH, which decreases in response to high circulating levels of sex steroids such as progesterone.
c. At menarche, there is a rapid rise in GnRH and thus LH secretion.
d. At menopause, there is an even greater rise in LH secretion.
3. Follicle Stimulating Hormone (FSH, or follitropin)
a. FSH stimulates folliculogenesis in the ovary and spermatogenesis in the testes.
b. FSH is regulated by GnRH, which is regulated by blood steroids.
c. FSH has sexual cycle rhythms in the female and circadian rhythms in the male.
4. NOTE: TSH, LH, & FSH contain two independent subunits of about 100 AAs: (Fig. 5.7)
a. The a-subunits are identical (so is the a -subunit in hCG) (92-96 AAs).
b. Their b-subunits have 35-82% homology. (LH & FSH have 82% homology)
C. THE STRESS-RELATED HORMONES
1. Proopiomelanocortin (POMC)
a. It is a common prohormone produced by cells of the anterior and intermediate lobes.
b. Fragments of this prohormone make ACTH, MSH, b -endorphin, & enkephalins.
2. Endorphins and enkephalins
3. Corticotropin (ACTH, or adrenocorticotropic hormone)
a. ACTH has 39 AA's, with the first 24 being the most important)
b. ACTH stimulates adrenal cortex to secrete glucocorticoids.
c. ACTH production is regulated basically the same way as for TSH (Fig. 13.9):
(i) CNS activity from stress impulses to the hypothalamus (increasing CRH)
(ii) ACTH feedback to hypothalamus.
(iii) glucocorticoid reduction of CRH production by the hypothalamus
(iv) glucocorticoid suppression of corticotrope secretion of ACTH.