Endocrinology
(Chapter 11)
Comp. Physiol.
Last revision: 10/15/98
Overhead: text (classic view of neural and endocrine regulatory systems)
Nervous and classical endocrine systems were for the longest time considered quite distinct entities.
Nervous system: rapid transient responses – Endocrine system: slow long-lasting effects.
Nervous system: Very short distance between effector cell and target cell – Endocrine system: Long distance between endocrine cell and target cell
We know now that this classical division does not fit with reality. There is really a continuum in the transition between nervous and endocrine systems, both in respect to the distance between effector and target and also regarding the duration of the response. The discovery of paracrine signaling certainly killed the idea that only neurotransmitters act over short distances.
Electric synaps - Chemical synaps - Varicosities - Neuroendocrine systems - Classical endocrine glands
Regulation of the activity of the gastrointestinal system in vertebrates is an example where it is really difficult to distiguish between nerve and hormone signaling. Several of the chemical signaling substances in the gut (e.g. CCK, substance P, VIP) are used both as hormones and as neurotransmitters.
Overhead: Withers 11-2 (integration between neural and endocrine systems)
Nervs and endocrine cells often work intimately together in the regulation of physiological systems. A typical neural reflex arc is rather similar to a 1st order neur-endocrine loop. In both cases the signaling substance is made by neurons that are located in the CNS. The practical difference is that the neurohormone is carried some distance in the extracellular fluid. There are 2nd and 3rd order neuroendocrine loops in which one or two of the links in the chain are made up by either neurons or endocrine glands. There are indeed several systems that are build upon a direct endocrine loop, in which the endocrine cells themselves sense the stimulus and react accordingly.
All these control loops occur commonly in vertebrates whereas first order neuroendocrine loops are dominating in most invertebrates. There is a trend in the invertebrate series of increasing complexity in the higher phyla in terms of the numbers of neuro- and classical hormones and the number of physiological functions they regulate.
Because we already have an excellent vertebrate endocrinology course in our school, the common lectures on endocrinology will focus primarily on invertebrates.
Coelenterata
Overhead: LD1-1 (hydra)
The coelenterates is the most primitive phylum with known endocrine system. This system consists exclusively of 1st order neuroendocrine loops. No classical endocrine glands are known.
What you see here is a diagram of a freshwater coelenterate, the Hydra.
These animals produce a surprisingly rich collection of chemical signaling substances, including a number of catecholamines, “vertebrate neuropeptides,” and some novel peptides.
Overhead: LD1-6 (neuropeptides in hydra)
This figure shows the distribution of several neuropeptides, we recognize in mammals, in the Hydra.
a) oxytosin/vasopressin
b) CCK
c) Substance P
d) Neurotensin
e) Bombesin
f) FMRFamide
I should say that the evidence for presence of these substances is based on crossreactivity with antibodies to the mammalian peptides. I do not know if any of these peptides have actually been isolated or their genes cloned from coelenterates.
Also, the biological effects of these neuropeptides in coelenterates remain enigmatic.
Overhead: text (head activator)
The most fundamental and potentially significant aspect of coelenterate endocrinology pertains to some peptides with morphogenic effects. A compound, named head activator peptide has been isolated and sequenced (Glp-Pro-Pro-Gly-Gly-Ser-Lys-Val-Ile-Leu-Phe). Interestingly, the identical peptide has been sequenced from mammals, including humans.
In the Hydra, the head activator influences head and bud formation, stimulating the elaboration of these structures when present in very low concentrations. It is also stimulating regeneration of the head region if it is severed. At the cellular level, the head activator functions as a mitogen or growth hormone, stimulating cells in G2 phase of the cell cycle to proceed through mitosis. There is also evidence for an involvement in control of determination of uncommitted stem cells.
Overhead: text (other neuroendocrine roles)
In addition to the effects of the head activator on tissue growth and differentiation it has been shown that the “vertebrate hormone” thyroxine promotes asexual reproduction through budding
There are other apparent endocrine functions in coelenterates as well. Some of these relate to feeding, but I will not get into that here.
Platyhelminthes
Overhead: A7-13 (Planaria)
Flatworms are more complex animals than the coelenterates, but they are still considered very primitive invertebrates. Like many lower invertebrates, most flatworms have a remarkable ability to regenerate lost body parts. This function has been worked on to some extent in an endocrinological context.
Overhead: LD2-6 (chemical changes after sectioning)
Flatworms have neurosecretory cells while no classical endocrine glands have been located. If you section off a piece of a planaria worm you will find increased activity in neurosecretory cells. There will also be a number of other chemical changes in the tissue surrounding the wound and this high activity will go on until the tissue is completely regenerated.
This figure illustrates some of this increased activity in the area of the wound.
Early 5-HT peak, parallel with increased adenylate cyclase activity and increased cAMP concentrations. Subsequently, there is a rise in intracellular Ca, which is believed to trigger DNA synthesis in planaria. While DNA synthesis and cell division may be directly attributed to 5-HT release, the increase in protein sysnthesis rate is probably the result of a different neurohormone. This other neurohormone may be dopamine because dopamine levels peak in the regenerate from 12 to 18 h, which correlates well with the increase in RNA synthesis, which starts 12 h after the sectioning and peaks at 18 h. Furthermore, dopamine inhibitors (haloperidol; fluphenazine) significantly delay regeneration of tissue.
Overhead: text (“vertebrate hormones in plathyhelminthes)
Several studies have investigated a number of turbellarians for the presence of hormones resembling those of mammals. In all these studies, the approach has been to use antibodies raised against mammalian hormones. Thus, rather than demonstrating the presence of the same hormone, the investigators have shown that there are molecules in turbellarians with antigenic determinants that resemble those of some mammalian hormones. Immunoreactivity against the following hormones have been detected:
· ACTH (primarily in margins of cerebral ganglia and nerve chords)
· Somatostatin (variable distribution)
· Met-encephalin
Any functions of these possible hormones remain elusive.
Mollusca
We are now taking a big step up to some advanced invertebrates, the mollusks. Neurosecretory hormones are important in 1st order responses and also some 2nd and 3rd order neuroendocrine systems. Much molluskan endocrine research has been devoted to the reproductive system. At present, the endocrine control of reproduction only of gastropods and cephalopods is known in some detail. Reproduction of mollusks is extremely diverse and its control is complicated. For example, many mollusks are protandrous hermaphrodites; young adults are males, followed by a phase during which both sexes are present simultaneously. In the final phase these snails have degenerated their male sex organs and become fully female.
Overhead: B10-10 (prosobranch)
This is a prosobranch, namely the marine keyhole limpet. In many aspects, prosobranchs are among the most primitive mollusks. The majority of the prosobranchs are protandrous hermaphrodies. Sex reversal from males to females has received a great deal of attention.
Overhead: LD mollusks 1-1 (reproductive systems); 1-2 (neuroendocrine system)
The juvenile gonad of protandric snails is bisexual. At sexual maturity, the gonads develop into testis under the influence of an androgenic neuroendocrine factor from cerebral ganglia. If this factor is absent, female gonads develop. Subsequent sex reversal is induced by a feminizing factor that also is released from the cerebral ganglia.
This is the “slipper shell” (Crepidula fornicata). The male accessory sex organs consist of a sperm duct, seminal vesicles, and external sperm groove, and a non-retractable penis. During sex reversal, these organs are rearranged into an oviduct, receptaculum seminis, uterus, and vagina. These changes occur independently of the conversion of testis into ovaries.
Differentiation of the penis is orchestrated by a neurohormone that is released from the right pedal ganglia under the influence of external ‘masculinizing’ stimulation. This hormone is released into the hemolymph and seems to accumulate in a specific haemal lacunae in the right tentacle.
The dedifferentiation or lysis of the penis, which occurs during the transition to the female phase, is induced by a neurohormone produced by neuroendocrine cells located in the mediodorsal area of the pleural ganglia. At the same time there is a negative control of the activity in the cells of the area in the pedal ganglion that produces the morphogenic factor responsible for penis differentiation.
Overhead: B10-16 (Pulmonates)
Pulmonate gastropods are more advanced than the prosobranchs and their endorcrine system is also more complex. We will look at the reproductive endocrinology of two suborders within the subclass pulmonata, stylomatophora and basommatophora. Stylommatophora include terrestrial snails and slugs, like Helix and Limax. Basommatophora are the most primitive pulmonates and they are primarily freshwater forms, such as Lymnaea. There are a few marine species, such as marine limpets, Siphonaria.
Overhead LD p.142 Fig. 1 (Lymnaea)
The drawing on top is an illustration of the basommatophoran, Lymnaea stagnalis.
Overhead W11-15 (Pulmonates reproductive endocrinology)
Like the Prosobranchs, the pulmonates are typically hermaphrodites. While the stylommatophorans (A) typically are protandrous hermaphrodites, basommatophoran species (B) are usually more simultaneous hermaphrodites (both sexes at the same time).
Stylommatophora
In stylomatophora, the ovotestis is connected to the male and female assessory sex organs by a hermatophroditic duct. The female and male reproductive tracts diverge and may, or may not, re-fuse to form a common genital opening. The female accessory sex organs are shown on top and the males below.
Dorsal body hormone (DBH) from the dorsal body (DB), which is under neural control of the cerebral ganglia (CG), promotes vitellogenesis and functioning of the female secondary sex organs. A secretion of the optic tentacles (OT) inhibit female sex cell development and promotes male sex cell differentiation. A female gonadal hormone (fgh) controls development of the female accessory sex organs and a male gonadal hormone (mgh) regulates development of the male accessory sex organs.
In basommatophoran snails the ovotestis is connected to the male and female accessory sex organs via a hermaphroditic duct. The female and male reproductive tracts diverge and the fertilization pocket may, or may not, re-fuse to form a common genital opening. Again, the female system is shown on top and the male organs below. Dorsal body hormone (DBH) from the dorsal body (DB) promotes female sex cell development, vitellogenesis, and the development of female accessory sex organs. Caudo-dorsal cell hormone (CDCH) from the caudo-dorsal cells promotes ovulation, oviposition, and egg-laying behaviour. A secretion of the lateral lobes (LL) promotes male sex cell maturation, most likely via stimulation of a neurohormone from neurosecretory cells (NSC).
Overhead: LD p. 178, Fig. 33 and 34
CDCH from Lymnaea has been cloned and sequenced. It forms a part of a larger precursor protein that is cleaved proteolytically into several neuropeptides. The entire gene spans >10kb. CDCH has been found to be homologous to the Egg-Laying-Hormone (ELH) in Aplysia. Also, other hormones encoded in this precursor show high degree of homology between Lymnaea and Aplysia.
Phylum Arthropoda
Class Crustacea
Overhead:Withers 11-16 (endocrine system of decapoda)
The crustacean endocrine system, like that of other higher invertebrates, has neurosecretory cells and some classical endocrine glands. The following are the principal endocrine areas.
1. The eye stalk contains a number of, so called, X-organs including medulla externa (me), sensory pore, medulla interna (mi), and medulla terminalis (mt) and the neurohemal organ, the sinus gland (sg). Axons from neurosecretory cells in the brain and other parts of the nervous system pass to the sinus gland via a neurosecretory tract.
2. The postcommisural organs receive axons from 4 neurosecretory cells in each side of the circumesophageal connectives: only one is shown on the left side.
3. The pericardeal organs are located over openings of branchiocardiac veins into the aorta: Numerous nerves run from the nervous system to the organs. The dorsal nerve of the heart (n. dors) and nerves to muscles (n. mot) are also shown.
4. The androgenic gland often is a vermiform mass of secretory cells attached to the distal portion of vas deferens. The ovaries secrete female sex steroids in many species.
5. The generalized neurosecretory system (except the eyestalk) consist of cerebral neurosecretory cells (ns 1-5) and thoracic ganglia neurosecretory cells. Axons of neurosecretory cells in all parts of the brain pass to the sinus gland, but only axons from ganglionic neurosecretory cells pass out through the pedal nerves.
6. The Y-organ is an endocrine gland without innervation; it is an ovoid disk of hypertrophied epidermis, which secretes molting hormone.
Overhead: Withers 11-17 (molting cycle)
Molting, that is the periodic shedding of the exoskeleton, is under endocrine regulation in crustaceans as well as in other arthropods. The event of exoskeleton shedding is termed, ecdysis, and names of the other phases in the molt cycle relate to ecdysis. Thus, the molt period starts with the proecdysis, which leads into the ecdysis. The period immediately following ecdysis is called metecdysis, and periods between molts are called anecdysis.
1. During proecdysis, the epidermis starts to separate from the old cuticule (exoskeleton) and the epidermal cells enlarge and begin to secrete the new exoskeleton. Minerals and macromolecules are reabsorbed from the old exoskeleton and temporarily stored elsewhere for later incorporation into the new exoskeleton. Amino acids are stored in the hemolymph, while Ca is deposited at various locations depending on species. The muscles of the major limb segments atrophy during proecdysis so that the limbs can be pulled out through the narrow basal segment at ecdysis. Regeneration of lost limbs also begins during proecdysis.
2. At ecdysis, the old exoskeleton cracks open, typically in the rear end, and the animal backs out of the old shell. When newly emerged, the new exoskeleton is pale and soft. In many species the molted animal eats the old exoskeleton to regain some of the minerals and other nutrients.